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Breast cancer is the most common type of cancer affecting women worldwide and its risk increases with age. Compared with other breast cancer subtypes, triple negative breast cancer (TNBC) behaves more aggressively, with earlier relapses and poorer survival outcomes. Although the incidence of TNBC decreases with age, it still affects about 10% of older women with breast cancer. The management of TNBC in older patients is particularly challenging as chemotherapy is the main treatment choice in both early and advanced diseases and older patients are often prone to increased treatment-related toxicities. This review highlights the specific considerations in this vulnerable group of patients and summarizes the current evidence for TNBC management in older adults from early to late stage of disease. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) became a treatment option in most tumor types and improved survival in patients with cancer in the last decade. Older patients with cancer are underrepresented in the pivotal clinical trials with ICIs. Older patients with cancer often have significant comorbidities and geriatric syndromes like frailty, which can complicate cancer care and treatment decisions. Frailty is among the most prevalent geriatric syndromes in patients with cancer and could lead to inferior survival and a higher risk of complications in patients treated with chemotherapy. However, the effect of frailty on the efficacy and safety of ICIs is understudied. This review focuses on the available evidence regarding the association between frailty and ICI efficacy and safety. Although the survival benefits of ICIs have generally been shown to be independent of age, the available real-world data has generally suggested higher rates of immune-related adverse events (irAEs) and treatment discontinuation in older patients. While international organizations recommend conducting a comprehensive geriatric assessment CGA to assess and address frailty before the start of anti-cancer therapies, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher is frequently used in clinical practice as synonymous with frailty, albeit with significant limitations. The available data has generally demonstrated diminished ICI efficacy in patients with an ECOG 2 or higher compared to patients with better performance status, while the incidence of high-grade irAEs were similar. Whilst evidence regarding outcomes with ICI in older patients and in those with sub-optimal performance status is growing, there is very limited data specifically evaluating the role of frailty with ICIs. These studies found a shortened overall survival, yet no evidence of a lower response rate to ICIs. These patients experienced more AEs, but they did not necessarily have a higher incidence of irAEs. [ABSTRACT FROM AUTHOR]

Malignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined with the longer life expectancy, this led to an increasing prevalence of melanoma in the older population. Recently, immune checkpoint inhibitors significantly improved the treatment of melanoma given their efficacy and tolerability profile. Two major classes of agents include the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors, such as ipilimumab, and the anti-programmed death-ligand 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab. Treatment of metastatic disease with immune checkpoint inhibitors demonstrated improved efficacy and better safety profiles compared to cytotoxic drugs and appears to be an attractive treatment option. Nevertheless, there is a need for tools designed to better predict which older patients will benefit from its use and who will experience toxicities related to the treatment. Current data do not show a major increase in toxicity rates in older patients. However, patients above 75 are often under-represented and those who are included are not representative of the general population of older patients, thereby also stressing the need for real-life data. Ongoing research is aiming at maximizing the potential treatment efficacy and developing novel immune-targeting modalities. Future studies should include older patients and assess geriatric domains in these older patients to better guide decision-making. This review discusses published clinical trials and where known, the efficacy and toxicity in older patients. Moreover, the clinical implications and future perspectives are discussed, with current recommendations for older patients, management of toxicities, and a proposal for an initial approach to the treatment of older patients with metastatic melanoma. [ABSTRACT FROM AUTHOR]

The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly. [ABSTRACT FROM AUTHOR]

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1–2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1–3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation. [Display omitted] • Undefined nodal RT indications for non-ALND patients with 1–2 positive SLN. • Undefined nodal RT indications when PST transforms cN1 disease into ypN0. • Undefined nodal RT indications for N + 1–3 mastectomized patients. • Optimal combinations of RT and immunotherapy are as yet unknown. • PBI after second BCS should be proposed for re-irradiation in low-risk patients. • Hyperthermia should be made available for superficial breast cancer recurrencesrecurrences. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (~10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy. [ABSTRACT FROM AUTHOR]

Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations. [ABSTRACT FROM AUTHOR]

The growing insights in the next-generation immunotherapy and the state-of-the-art advancement in targeted-agents significantly improved clinical outcome of cancer patients by pointing towards a unexplored Achilles' heel. Novel toxicity profiles have been uncovered, representing unmet medical needs. Thus, a panel of expert provide comprehensive pharmacological and clinical evidence, to provide a patient-tailored approach to metabolic adverse events associated with novel anti-cancer treatments. Prompted by the need of a multidisciplinary cooperation, a working group of Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD) and Società Italiana Farmacologia (SIF) examined the available literature data. The identification of patient risk profile and the characterization of metabolic effects of novel anti-tumour drugs is clearly a clinical challenge that can be addressed by a multidisciplinary clinical approach. Therefore, this review pinpoints the relevance of the challenging profiling of the patient suffering from dysmetabolic conditions induced by the novel therapeutics in medical oncology. [ABSTRACT FROM AUTHOR]

[Display omitted] • This article focuses on immunotherapy, a new treatment for tumors with low side effects, and suggests the direction of improvement. • Programmed cell death (apoptosis, necroptosis, ferroptosis, pyroptosis and autophagy) induced by nanomedicine was reviewed in this paper. • This paper focuses on the role of nanomedicine-induced programmed cell death in cancer therapy. • This article reviews the improvement of the limitations of immunotherapy with nanomedicine-induced PCD. • In this paper, the development prospect of tumor therapy and immunotherapy of PCD mediated by nanomedical drugs is prospected. There has been widespread concern about the high cancer mortality rate and the shortcomings of conventional cancer treatments. Immunotherapy is a novel oncology therapy with high efficiency and low side effects, which is a revolutionary direction for clinical oncology treatment. However, its clinical effectiveness is uneven. Based on the redefinition and reclassification of programmed cell death (PCD) (divided into necroptosis, ferroptosis, pyroptosis, and autophagy), the role of nanomedicine-induced PCD in cancer therapy has also received significant attention. Clinical and preclinical studies have begun to combine PCD with immunotherapy. In this article, we present recent research in tumor immunotherapy, provide an overview of how nanomedicine-induced PCD is involved in tumor therapy, and review how nanomedicine-induced PCD can improve the limitations of immunotherapy to enhance tumor immunotherapy. The future development of nanomedicine-mediated PCD tumor therapy and tumor immunotherapy is also proposed Key scientific concepts of overview Nanomedicine-induced PCD is a prospective method of tumor immunotherapy. Nanomedicines increase tumor site penetration and targeting ability, and nanomedicine-mediated PCD activation can stimulate powerful anti-tumor immune effects, which has a good contribution to immunotherapy of tumors. [ABSTRACT FROM AUTHOR]

Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials. • Immunotherapy added to chemotherapy improves disease-free and overall survival in advanced and metastatic endometrial cancer. • Endometrial cancer is the malignancy with the highest prevalence of MMRd/MSI-H. • MMRd/MSI-H is an agnostic biomarker suggesting the efficacy of immunotherapy. • Immunotherapy plus chemotherapy improves progression-free survival even in the MMR-proficient population. [ABSTRACT FROM AUTHOR]

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Whether prostate brachytherapy (BT) results in opportunistic biological changes that can improve clinical outcomes is not well studied. We sought to investigate the impact of prostate BT on the immune system. A scoping review was performed using PubMed/Scopus for papers published between 2011-2021. Search terms were "brachytherapy" AND "immune" AND "prostate". A total of 81 records were identified and 6 were selected for further review. 2 low-dose-rate BT papers (n=68) evaluated changes in the peripheral blood following I-125 monotherapy. Both showed significant increases in peripheral CD3+ and CD4+ T cells post-BT. One also demonstrated significant increases in Treg subsets up to 150 days post-BT. 4 high-dose-rate (HDR) studies (n=37) were identified, and all were done in combination with EBRT. The largest study (n=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature when comparing a pre-BT biopsy to one prior to a second HDR fraction. Prostate BT can invoke an immune activating phenotype; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to promote synergy between BT and the immune system. [ABSTRACT FROM AUTHOR]

Imaging mass cytometry (IMC) is a new technology integrating mass spectrometry, high-resolution laser ablation and immunohistochemistry/cytochemistry. A unique high-dimensional perspective comprehensively and accurately depicts the complex interaction of phenotype, signalling pathway and tumour microenvironment and is widely used in solid tumours. However, the application scenarios of IMC in basic medicine and clinical research in solid tumours lack systematic introduction and classification. This paper reviews the application of IMC in depicting the panorama of the tumour microenvironment, revealing tumour spatial heterogeneity, clarifying tumour pharmacological mechanisms, assisting in new drug development, and dynamically evaluating the efficacy of immunotherapy in solid tumours. • IMC is a new technology integrating mass spectrometry, high-resolution laser ablation and immunohistochemistry. • This paper reviews the application of IMC in basic laboratory studies, preclinical studies and clinical observations in solid tumours. • It can depict the complex phenotypes in tissue and tumour microenvironment. • IMC is a powerful tool for solid tumour transformation research and precision treatment as new technology. • The existing research cases are classified and summarized, meanwhile the clinical trials using IMC are listed. [ABSTRACT FROM AUTHOR]

A paradigm shift in cancer treatment occurred with the advent of immune checkpoint inhibitors (ICI). ICI therapy has improved tumor response and increased overall survival in patients with solid tumors and hematologic malignancies. While ICI therapy has improved overall patient outcomes in oncology, it has also introduced novel adverse effects called immune-related adverse effects (irAEs). Studies have shown that the development of irAEs is associated with improved overall survival, but certain irAEs like pneumonitis and myocarditis are life threatening, and could result in death if not identified and treated early. Therefore, it is important for radiologists to be aware of complications arising from ICI administration, especially those related to the heart and lungs as they are associated with greater mortality. This paper will review the imaging features of cardiothoracic toxicities, recurrent and chronic irAEs, and atypical tumor responses associated with irAEs. • Imaging plays a key role in identifying the cardiothoracic complications of immunotherapy. • Some cardiothoracic complications are associated with high mortality and imaging plays a crucial role in their diagnosis. • Early detection of complications can prompt early initiation of treatment, allowing patients to continue immunotherapy. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) represent cellular chaperones that are classified into several families, including HSP27, HSP40, HSP60, HSP70, and HSP90. The role of HSPs in the cell includes the facilitation of protein folding and maintaining protein structure. Both processes play crucial roles during stress conditions in the cell such as heat shock, degradation, and hypoxia. Moreover, HSPs are important modulators of cellular proliferation and differentiation, and are strongly associated with the molecular orchestration of carcinogenesis. The expression and/or activity of HSPs in cancer cells is generally abnormally high and is associated with increased metastatic potential and activity of cancer stem cells, more pronounced angiogenesis, downregulated apoptosis, and the resistance to anticancer therapy in many patients. Based on the mentioned reasons, HSPs have strong potential as valid diagnostic, prognostic, and therapeutic biomarkers in clinical oncology. In addition, numerous papers describe the role of HSPs as chaperones in the regulation of immune responses inside and outside the cell. Importantly, highly expressed/activated HSPs may be inhibited via immunotherapeutic targets in various types of cancers. The aim of this work is to provide a comprehensive overview of the relationship between HSPs and the tumor cell with the intention of highlighting the potential use of HSPs in personalized cancer management. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has shown increased overall survival in a wide range of cancer types with the associated risk of developing severe immune-mediated adverse events, commonly involving the gastrointestinal tract. The aim of this position statement is to provide an updated practice advice to the gastroenterologists and oncologists on the diagnosis and management of ICI-induced gastrointestinal toxicity. The evidence reviewed in this paper includes a comprehensive search strategy of English language publications. Consensus was reached using a three-round modified Delphi methodology and approved by the members of the Belgian Inflammatory Bowel Disease Research and Development Group (BIRD), Belgian Society of Medical Oncology (BSMO), Belgian group of Digestive Oncology (BGDO), and Belgian Respiratory Society (BeRS). The management of ICI-induced colitis requires an early multidisciplinary approach. A broad initial assessment is necessary (clinical presentation, laboratory markers, endoscopic and histologic examination) to confirm the diagnosis. Criteria for hospitalisation, management of ICIs, and initial endoscopic assessment are proposed. Even if corticosteroids are still considered the first-line therapy, biologics are recommended as an escalation therapy and as early treatment in patients with high-risk endoscopic findings. • An early multidisciplinary approach for management of ICI-induced colitis is necessary. • Endoscopic evaluation should be performed to confirm diagnosis and adapt management. • Biologics are proposed as early treatment if high-risk endoscopic findings are present. • Re-challenge with ICIs can be considered in some specific situations. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) and targeted therapies (TT) have significantly improved disease control and survival in people with stage III and IV cutaneous melanoma. Understanding the impact of therapy on health-related quality of life (HRQL) is vital for treatment decision-making and determining targets for supportive care intervention. We conducted a mixed-methods systematic review to synthesise the impact of ICIs and TT on all domains of HRQL in these populations. A systematic literature search was conducted in April 2022 on MEDLINE, PsycINFO, Embase and the Cochrane Central Register of Controlled Trials. Quantitative and qualitative data relevant to the review question were extracted and synthesised in tables according to setting (adjuvant versus metastatic), treatment type (ICI versus TT) and HRQL issue. Twenty-eight papers describing 27 studies were included: 15 randomised controlled trials (RCTs), four cohort studies, four single arm cross-sectional studies, two qualitative studies, one case control study and one mixed-methods study. In four studies of people with resected stage III melanoma, adjuvant pembrolizumab and dabrafenib-trametinib did not clinically or statistically change HRQL compared to baseline. In 17 studies of people with unresectable stage III/IV melanoma, inconsistencies in the impact of ICI on symptoms, functioning and overall HRQL were noted across different study designs. TT was associated with improvements in symptoms, functioning and HRQL across six studies. This review highlights the key physical, psychological and social issues experienced by people with stage III and IV melanoma treated with ICI and TT. Inconsistencies in the impact of ICI on HRQL were observed in different study designs. This highlights the need for treatment-specific patient-reported outcome measures for determining the impact of these therapies on HRQL and real-world data to inform treatment decision-making and appropriate supportive care interventions. • In resected stage III melanoma, adjuvant therapy didn't alter health-related quality of life (HRQL) versus baseline. • In unresectable stage III/IV melanoma, immune checkpoint inhibitors had a variable impact on HRQL. • TT improved symptoms, functioning and HRQL across multiple studies. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a serious disease endangering the health of patients, and the application of immunotherapy in HNSCC is gradually emerging. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of immunotherapy for HNSCC. Publications related to immunotherapy for HNSCC from 2002 to 2021 were searched in the Web of Science Core Collection database. The software VOSviewers, CiteSpace, and the R package 'bibliometrix' were used to perform this bibliometric analysis. A total of 1297 publications were from 63 countries, led by the USA and China. The number of publications related to immunotherapy for HNSCC has increased rapidly from 2015. University of Pittsburgh and The University of Texas M.D. Anderson Cancer Center are the main research institutions. Oral Oncology is the most popular journal in this field, and the Journal of Clinical Oncology is the most highly co-cited journal. These publications were from 7569 authors, with Robert L. Ferris publishing the most papers and being the most frequently co-cited. Clinical trials related to nivolumab and pembrolizumab have attracted wide attention. 'Immune checkpoint inhibitors', 'human papillomavirus', 'programmed cell death-ligand 1', and 'programmed cell death protein 1' are the main keywords of emerging research hotspots. This study presents a comprehensive summary of the trends and development of immunotherapy for HNSCC, identifies the research frontier and hotspot direction, and could provide a valuable reference for researchers in this field. [ABSTRACT FROM AUTHOR]

The limitations of traditional cancer treatments are driving the creation and development of new nanomedicines. At present, with the rapid increase of research on nanomedicine in the field of cancer, there is a lack of intuitive analysis of the development trend, main authors and research hotspots of nanomedicine in the field of cancer, as well as detailed elaboration of possible research hotspots. In this review, data collected from the Web of Science Core Collection database between January 1st, 2000, and December 31st, 2021, were subjected to a bibliometric analysis. The co-authorship, co-citation, and co-occurrence of countries, institutions, authors, literature, and keywords in this subject were examined using VOSviewer, Citespace, and a well-known online bibliometrics platform. We collected 19,654 published papers, China produced the most publications (36.654%, 7204), followed by the United States (29.594%, 5777), and India (7.780%, 1529). An interesting fact is that, despite China having more publications than the United States, the United States still dominates this field, having the highest H-index and the most citations. Acs Nano, Nano Letters, and Biomaterials are the top three academic publications that publish articles on nanomedicine for cancer out of a total of 7580 academic journals. The most significant increases were shown for the keywords "cancer nanomedicine", "tumor microenvironment", "nanoparticles", "prodrug", "targeted nanomedicine", "combination", and "cancer immunotherapy" indicating the promising area of research. Meanwhile, the development prospects and challenges of nanomedicine in cancer are also discussed and provided some solutions to the major obstacles. [Display omitted] • Data of current nanomedicine in cancer were collected from the Web of Science. • Collected data were systematically analyzed through bibliometric analysis. • Many keywords of nanomedicine in cancer were intuitively analyzed. • Hotspots, emerging frontiers and trend of nanomedicine in cancer were investigated. • Development prospects and challenges of nanomedicine in cancer were discussed. [ABSTRACT FROM AUTHOR]

Radiotherapy is often used to improve cancer immunotherapy outcomes. While there are both pre-clinical and clinical data supporting this approach, there are also significant challenges. One key challenge is that not all patients have tumors that can be easily treated with radiotherapy due to potential normal tissue toxicity and prior treatment. In addition, it is difficult to control the tumor microenvironment to promote the immune response after radiosurgery. To overcome these challenges, we hypothesize that we can engineer cancer metastasis and utilize irradiated engineered tumor cells as a personalized cancer vaccine to improve cancer immunotherapy. Herein, we report the development of engineered lung metastasis using decellularized rat lung tissue. Using the B16F10 melanoma tumor model, we showed that radiotherapy-treated engineered metastases are highly effective in improving cancer immunotherapy responses and more effective than in vivo metastasis. Our work has demonstrated the potential of applying tissue engineering to cancer immunotherapy. Combination of radiation and immunotherapy are an effective way to treat metastasis. Despite their success, long term response still remains low. Tumor microenvironment evading the immune response, normal tissue toxicity to radiation and inaccessibility to radiosurgery are some of the limitations. To overcome these challenges, in this paper we present with data supporting the use of high dose radiation treated ex vivo engineered B16F10 metastasis model using decellularized lung scaffolds. These engineered metastases closely mimic the in vivo tumors and when given into tumor bearing mice along with check point inhibitors are highly effective in improving the cancer immunotherapy response. [Display omitted] [ABSTRACT FROM AUTHOR]

The occurrence and development of tumors are closely associated with abnormalities in the immune system's structure and function, with tumor immunotherapy being intricately linked to the tumor microenvironment (TME). Early studies on lymphocytes within the TME primarily concentrated on T cells. However, as research has advanced, the multifaceted roles of tumor-infiltrating B cells (TIL-Bs) in tumor immunity, encompassing both anti-tumor and pro-tumor effects, have garnered increasing attention. This paper explored the composition of the TME and the biological characteristics of TIL-Bs, investigating the dual roles within the TME to offer new insights and strategies for tumor immunotherapy. [Display omitted] • Dual roles of tumor-infiltrating B cells in tumor microenvironment: anti-tumor and pro-tumor effects. • Tumor-infiltrating B cells boost anti-tumor immunity via antigen presentation, antibody production, cytokine secretion, etc. • Regulatory B cells aid tumor immune evasion by releasing suppressive cytokines, specific antibodies, and metabolites. • Insights into Tumor-infiltrating B cells may offer potential new targets for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In the contemporary landscape of oncology, immunotherapy, represented by immune checkpoint blockade (ICB) therapy, stands out as a beacon of innovation in cancer treatment. Despite its promise, the therapy's progression is hindered by suboptimal clinical response rates. Addressing this challenge, the modulation of the NLRP3 inflammasome-GSDMD-mediated pyroptosis pathway holds promise as a means to augment the efficacy of immunotherapy. In the pathway, the NLRP3 inflammasome serves as a pivotal molecular sensor that responds to inflammatory stimuli within the organism. Its activation leads to the release of cytokines interleukin 1β and interleukin 18 through the cleavage of GSDMD, thereby forming membrane pores and potentially resulting in pyroptosis. This cascade of processes exerts a profound impact on tumor development and progression, with its function and expression exhibiting variability across different tumor types and developmental stages. Consequently, understanding the specific roles of the NLRP3 inflammasome and GSDMD-mediated pyroptosis in diverse tumors is imperative for comprehending tumorigenesis and crafting precise therapeutic strategies. This review aims to elucidate the structure and activation mechanisms of the NLRP3 inflammasome, as well as the induction mechanisms of GSDMD-mediated pyroptosis. Additionally, we provide a comprehensive overview of the involvement of this pathway in various cancer types and its applications in tumor immunotherapy, nanotherapy, and other fields. Emphasis is placed on the feasibility of leveraging this approach to enhance ICB therapy within the field of immunotherapy. Furthermore, we discuss the potential applications of this pathway in other immunotherapy methods, such as chimeric antigen receptor T-cell (CAR-T) therapy and tumor vaccines. In our review, we systematically elucidate the composition and activation pathway of the NLRP3 inflammasome, along with the characteristics and activation pathway of GSDMD-mediated pyroptosis. We comprehensively delineate the dual effects of the three pivotal factors on tumors within the NLRP3 inflammasome-GSDMD-mediated pyroptosis pathway: inflammatory mediators, self-components, and pyroptosis. Furthermore, NLRP3 inflammasome-GSDMD-mediated pyroptosis is deeply involved in tumor therapy, especially in the emerging field of nano-therapy. The combination of these therapeutic approaches with immunotherapy provides new perspectives on cancer immunotherapy. [Display omitted] • Our paper elucidates the composition and activation pathways of the NLRP3 inflammasome and GSDMD-mediated pyroptosis. • We detail the dual effects of key factors influencing tumors within the NLRP3 inflammasome-GSDMD-mediated pyroptosis pathway. • NLRP3 inflammasome-GSDMD-mediated pyroptosis plays a crucial role in tumor therapy, particularly in nanotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors. [ABSTRACT FROM AUTHOR]

Dual programmed cell death-1 and vascular endothelial growth factor pathway inhibition is the novel standard of care for patients with unresectable hepatocellular carcinoma. Direct comparisons between first-line treatments are lacking. We conducted a literature search in MEDLINE (https://pubmed.ncbi.nlm.nih.gov), the Cochrane library (https://www.cochranelibrary.com) and Embase (www.embase.com) between January 2007 and February 2022. We included phase III randomised controlled trials that tested immune-checkpoint inhibitors or tyrosine kinase inhibitors, including sorafenib, lenvatinib and donafenib, and evaluated as primary end-point overall survival (OS) or progression-free survival (PFS). Studies testing loco-regional therapies were excluded. The primary end-point was to compare the efficacy of first-line options in terms of OS and PFS. We extracted Hazard ratios (HR) and 95% confidence intervals (95% CI) for OS and PFS and performed a frequentist network meta-analysis with fixed effect multivariable meta-regression models. The research protocol was registered in PROSPERO, an international prospective register of systematic reviews (registration code CRD42022312489). Literature review yielded 13709 results, after duplicates removal and exclusion of not relevant studies, 70 papers were available for screening. After full-text review, 9 studies were eligible for analysis. Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events. • Immune-checkpoint inhibitor plus anti-vascular endothelial growth factor agent provide the highest reduction in the risk of death in hepatocellular carcinoma. • The efficacy of immune-checkpoint inhibitor plus anti-vascular endothelial growth factor is similar to that of dual checkpoint inhibition. • The efficacy of combination strategies comes at the expense of higher toxicity. • Nivolumab is associated with the lowest risk of adverse events. [ABSTRACT FROM AUTHOR]

• To our knowledge, it is the first study to gather, in a comprehensive manner, employment data on LC patients. • Being employed is correlated with a better quality of life regarding physical functioning. • On a societal perspective, RTW of LC patients represents a priority as the costs associated with work loss and reduction of productivity have a significant impact. • New drug therapies may increase the patients' chance of resuming their former activities (including working). • Therefore, potentially reduce the economic burden they place on healthcare systems. The aim of this systematic review is to identify, in a comprehensive manner, the impact of lung cancer on the employment status of survivors. The Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA) statement was used as a formal guideline. The systematic review includes scientific papers published between January 2000 and October 2018. The search strategy queried the database MEDLINE. Inclusion criteria comprised: (1) inclusion of patients diagnosed with lung cancer (LC) (2); assessment of employment status or employment outcomes or work adjustments or return to work (3); inclusion of scientific papers published in peer-reviewed journals (4); inclusion of articles written either in English or in French. Literature reviews were not included. A total of 642 scientific papers were retrieved. Twenty-three articles were included in the systematic review: 5 longitudinal studies and 18 cross-sectional studies. LC survivors are 2–3 times more likely to be unemployed as compared with control groups. Previous studies highlight a median duration of sickness absence increased for LC survivors compared to control groups. The strongest decline in earnings was observed among LC survivors as compared to other cancer types. LC is associated with a significant impact on employment of patients. The promising results of recent therapeutic strategies could lead to a better social and professional prognosis. A reduction of indirect costs is to be expected. [ABSTRACT FROM AUTHOR]

Background Intra-pleural bacteria are effective pleurodesis agents in malignant pleural effusions. However, their relationship with survival is unclear. Objectives We undertook a comprehensive, structured evaluation of survival outcomes in adults with malignant pleural effusions treated with intra-pleural bacterial products. Data sources Medline, Embase, Cochrane library, Clinical Trials Registers and Open Grey. Study eligibility criteria, participants, and interventions Randomised controlled trials and non-randomised comparative studies were included, if the population included adults with malignant pleural effusions. Interventions of interest were any intra-pleural bacterial product, compared with placebo, alternative intra-pleural drug, or no treatment. Survival outcomes were collected. Study appraisal and synthesis methods: Two reviewers independently screened studies for eligibility, assessed papers for risk of bias and extracted data. Narrative synthesis was performed as high heterogeneity between studies precluded meta-analysis. Results 631 studies were identified, of which 14 were included. All were at high or unclear risk of bias in at least one domain. Six studies reported a survival benefit associated with intra-pleural bacterial products, whilst 8 reported no difference. Non-randomised studies and studies published prior to 2000 were more likely to report survival benefits. Limitations There was high heterogeneity between studies, which limited the generalisability of findings. Publication bias may have affected the review as five full-text papers were unobtainable, and survival outcomes were missing in a further five. Conclusions There is a lack of high quality evidence regarding the relationship between intra-pleural bacterial products and survival. Implications of key findings: Well-designed, prospective randomised trials are needed, to determine whether intra-pleural bacterial products can improve survival in pleural malignancy. PROSPERO registration number CRD42017058067. [ABSTRACT FROM AUTHOR]

• Aptamer-mediated nanomedicines could enhance the accuracy of drug delivery and target drug delivery to tumor sites, reducing side effects. • Aptamer-mediated photodynamic therapy could more precisely deliver photosensitizers to tumor cells, reducing toxicity to normal tissues. • Aptamer-mediated photothermal therapy could enable the light source to more accurately locate and convert light energy into heat energy, causing local temperature rise, thereby eliminating cancer cells and effectively reducing the adverse effects on normal tissues. • Immunotherapy combined with aptamers could more accurately identify and modulate immune cells in the tumor microenvironment, enhancing anti-tumor immune responses and protecting normal tissues. The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients. [ABSTRACT FROM AUTHOR]

Adoptive T cell therapy has undergone remarkable advancements in recent decades; nevertheless, the rapid and effective ex vivo expansion of tumor-reactive T cells remains a formidable challenge, limiting their clinical application. Artificial antigen-presenting substrates represent a promising avenue for enhancing the efficiency of adoptive immunotherapy and fostering T cell expansion. These substrates offer significant potential by providing flexibility and modularity in the design of tailored stimulatory environments. Polydimethylsiloxane (PDMS) silicone elastomer stands as a widely utilized biomaterial for exploring the varying sensitivity of T cell activation to substrate properties. This paper explores the optimization of PDMS surface modification and formulation to create customized stimulatory surfaces with the goal of enhancing T cell expansion. By employing soft PDMS elastomer functionalized through silanization and activating agent, coupled with site-directed protein immobilization techniques, a novel T cell stimulatory platform is introduced, facilitating T cell activation and proliferation. Notably, our findings underscore that softer modified elastomers (Young' modulus E∼300 kPa) exhibit superior efficacy in stimulating and activating mouse CD4+ T cells compared to their stiffer counterparts (E∼3 MPa). Furthermore, softened modified PDMS substrates demonstrate enhanced capabilities in T cell expansion and Th1 differentiation, offering promising insights for the advancement of T cell-based immunotherapy. [Display omitted] • Chemically modified layers and Protein A enhance antibody density and stability. • Softer elastomers better stimulate CD4+ T cells compared to stiffer ones. • Softened PDMS substrates enhance T cell expansion and Th1 differentiation. • Study shows surface chemistry and mechanical cues influence T cell behavior. [ABSTRACT FROM AUTHOR]

• Ultrasound combined with tumor immunotherapy made encouraging new progress in both basic research and clinical treatment. • Ultrasound can increase the delivery of immunomodulatory substances and enhance the effect of immunotherapy. • Ultrasound can be used to improve the body's immune response to tumors. Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field. [ABSTRACT FROM AUTHOR]

To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676) In this paper, we show, for the first time, that treatment with a combination of BCG and Pembrolizumab for high-grade non-muscle invasive bladder cancer poses no significant changes in urinary bother, patient quality of life, or urinalysis based on 2-year follow-up data of a cohort of patients enrolled in the Phase I dose escalation trial NCT02324582. A phase III trial has since opened to study further this combination's efficacy and safety (KEYNOTE-676). Our findings are a new addition to the literature in that they support an additional option in treatment for patients who cannot elect for curative surgical management without posing significant disruption to day-to-day life. [ABSTRACT FROM AUTHOR]

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment. The integration of drug delivery systems with inhibitors that target STAT3 effectively impedes the STAT3 signaling pathway in cancer. Achieved through modalities such as chemotherapy, immunotherapy, and targeted therapy, this integration consequently amplifies the therapeutic efficacy. [Display omitted] [ABSTRACT FROM AUTHOR]

• E-MPBs shows sustained cellular uptake by microglia. • E-MPBs exhibits anti-ROS and anti-inflammation properties against M1 microglia. • E-MPBs develops a novel nanoplatform for SCI. Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H 2 O 2 -induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible. [ABSTRACT FROM AUTHOR]

• Cancer patients may develop endocrine immune-related adverse events during Immune checkpoint inhibitors (ICI) treatment. • Awareness of development and management of endocrinopathies under ICI may improve patient survival and quality of life. • This is a multi-specialty, simple and easily applicable endocrine-metabolic assessment checklist for cancer patients on ICI. Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy. [ABSTRACT FROM AUTHOR]

Inflammation is not the only cause of depression and cannot explain its entire pathophysiology, but it is an important pathogenic factor that explains one possible mechanism of depression, with the kynurenine (KYN) pathway of tryptophan at its center. In particular, greater impairment seems to exist in the KYN pathway in inflammation-induced depression related to immunotherapy, autoimmune disease, and infection. In patients with these conditions, immunopharmacology is likely to be an important therapy. To develop this therapy, clear evidence of the immune-KYN pathway must be established via multiple types of experiments. This paper reviews the body of evidence, not only for the action of tryptophan (TRY) and consequent serotonin depletion, but also for the detrimental effects of TRY catabolites and the key enzymes in the KYN pathway that play important roles in the pathophysiology of inflammation-induced depression. In addition, this paper explores a potential treatment strategy for inflammation-induced depression using KYN metabolism. [ABSTRACT FROM AUTHOR]

• ImmunoPET is a potential biomarker for patient selection to immunotherapy. • Patient response classification differs with tumor measurement strategy. • MPM tumor volumetry predicts patient survival and outperforms CT volumetry. • CT image texture has potential to differentiate among MPM tumor histologies. • Skeletal muscle loss in chemotherapy patients demonstrates prognostic potential. Imaging of mesothelioma plays a role in all aspects of patient management, including disease detection, staging, evaluation of treatment options, response assessment, pre-surgical evaluation, and surveillance. Imaging in this disease impacts a wide range of disciplines throughout the healthcare enterprise. Researchers and clinician-scientists are developing state-of-the-art techniques to extract more of the information contained within these medical images and to utilize it for more sophisticated tasks; moreover, image-acquisition technology is advancing the inherent capabilities of these images. This paper summarizes the imaging-based topics presented orally at the 2021 International Conference of the International Mesothelioma Interest Group (iMig), which was held virtually from May 7–9, 2021. These topics include an update on the mesothelioma staging system, novel molecular targets to guide therapy in mesothelioma, special considerations and potential pitfalls in imaging mesothelioma in the immunotherapy setting, tumor measurement strategies and their correlation with patient survival, tumor volume measurement in MRI and CT, CT-based texture analysis for differentiation of histologic subtype, diffusion-weighted MRI for the assessment of biphasic mesothelioma, and the prognostic significance of skeletal muscle loss with chemotherapy. [ABSTRACT FROM AUTHOR]

The crosstalk between the transformed tumoral cells and their microenvironment is a key aspect for pancreatic ductal adenocarcinoma (PDAC) progression. This molecular dialog is intensively studied because it may result in an efficient therapeutic target. Contrary to this near microenvironment, the stromal portion in direct contact with the transformed cells, a far microenvironment, placed at the periphery of the tumor mass, produces factors signaling tumors. Among these factors, REG3β, produced by this part of the pancreas, is an important factor in promoting tumor progression. This paper demonstrated that targeting REG3β protein with specific antibodies limits the PDAC tumor growth in an orthotopic, syngeneic mice model induced by injection of Panc02 cells. Then, we showed that CTGF is over-expressed in response to REG3β in PDAC-derived cells. Moreover, inactivation of REG3β by treating tumors with anti-REG3β antibodies results in a strong decrease of CTGF in PDAC tumors. Lastly, we demonstrated that forced expression of CTGF in xenografted Panc02 cells abolishes the therapeutic effect of the anti-REG3β antibody treatment. Altogether, these results indicate that the effect of REG3β in promoting PDAC progression is mediated by CTGF over-activation. Thus, REG3β is a promising therapeutic target to treat PDAC with an original rationale. In conclusion, we demonstrated that the far microenvironment is essential for PDAC progression by producing active secretory factors, and some of them could be used as therapeutic targets. [ABSTRACT FROM AUTHOR]

Rasmussen Encephalitis (RE) is classically described as a childhood encephalopathy due to a unilateral inflammation of the cerebral cortex with a presumed immune-mediated pathophysiological basis. Unusual variant forms, including adolescent and adult-onset RE have been described but there is still a doubt whether these atypical cases correspond to classical RE patients. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing late onset RE to assess (i) the positivity rate of classical childhood-onset diagnostic criteria for RE in late-onset RE, (ii) the specific clinical and radiological features that could help earlier diagnosis and therapeutic interventions, (iii) the arguments for an autoimmune pathophysiology including (iiia) the association with autoimmune markers or diseases and (iiib) the effects of immunomodulatory or immunosuppressive treatments. A total of 50 papers were considered. We identified 102 late-onset RE patients with a sex ratio of 8 women for 2 men. 67% fulfilled the consensus diagnostic criteria for RE. As compared to classical RE, the late-onset RE patients exhibited: i) more frequent focal complex partial seizures, ii) less frequent epilepsia partialis continua throughout evolution, iii) a slower evolution with a delayed occurrence of cortical deficit, iv) less cognitive deterioration and v) a better outcome. A specific association with autoimmune markers or diseases was not found. Immunomodulatory therapies, even performed in a late stage, improved late-onset RE patients in 61% of cases. This review proves that late-onset RE is a reality with specific clinical and radiological features. The good response to immunomodulatory treatments brings further arguments for an immune-regulated process. [ABSTRACT FROM AUTHOR]

A high level of concern is placed on the storage, handling, transportation, and distribution of vaccines and other pharmaceutical products, particularly those that are time and temperature sensitive. While active and passive cooling equipment and monitoring devices are important, it is the various personnel responsible for executing and writing procedures, designing and operating systems, and investigating problems and helping prevent them who are paramount in establishing and maintaining a “cold chain” for time and temperature sensitive pharmaceutical products (TTSPPs). These professionals must possess the required competencies, knowledge, skills and abilities so they can effectively perform these activities with appropriate levels of expertise. These are complex tasks that require the development of higher cognitive skills that cannot be adequately addressed through professional development opportunities based on simple information delivery and content acquisition. This paper describes two unique learning solutions (one on a bus called the “wheels course” and the other online called “e-learning”) that have been developed by WHO Global Learning Opportunities (WHO/GLO) to provide participants with opportunities not just to learn about cold chain systems or vaccine management, but, rather, to develop high levels of expertise in their respective fields through experiential and authentic learning activities. In these interactive learning environments, participants have opportunities to address real-life situations in contexts similar to what they may face in their own work environments and develop solutions and critical thinking skills they can apply when they return to their jobs. This paper further delineates the managerial and operational vaccine management functions encompassed in these two unique learning environments. The paper also describes the alignment of the objectives addressed in the “wheels course” and the e-learning version with effective vaccine management (EVM) criteria as prescribed by WHO. The paper concludes with an example of a real world product developed by course graduates (specifically a decision tree that is now used by some national programmes). These types of products, valuable in their own right, often emerge when learning environments based on authentic learning principles are designed and implemented as they were by WHO/GLO. [ABSTRACT FROM AUTHOR]

• The importance of drug delivery timing and dosage in chemoimmunotherapy has been studied on a new model proposed in the paper. • The optimal controller is designed to reduce cancer cells for a lower dosage of immunotherapy and a fixed dosage of chemotherapy. • The suggested optimal timing and dosage of immunotherapy is able to reduce cancer cells, with less amount of drug injection compared to a fixed protocol. • The achievement of this paper could be the basis for designing new clinical trials. There are various approaches to control a mathematical dynamic of cancer, each of which is suitable for a special goal. Optimal control is considered as an applicable method to calculate the minimum necessary drug delivery in such systems. In this paper, a mathematical dynamic of cancer is proposed considering tumor cells, natural killer cells, CD8+ T cells, circulating lymphocytes, IL-2 cytokine and Regulatory T cells as the system states, and chemotherapy, IL-2 and activated CD8+ T cells injection rate as the control signals. After verifying the proposed mathematical model, the importance of the drug delivery timing and the effect of cancer cells initial condition are discussed. Afterwards, an optimal control is designed by defining a proper cost function with the goal of minimizing the number of tumor cells, and two immunotherapy drug amounts during treatment Results show that inappropriate injection of immunotherapy time schedule and the number of initial conditions of cancer cells might result in chemoimmunotherapy failure and auxiliary treatment must be prescribed to decrease tumor size before any treatment takes place. The obtained optimal control signals show that with lower amount of drug delivery and a suitable drug injection time schedule, tumor cells can be eliminated while a fixed immunotherapy time schedule protocol fails with larger amount of drug injection. This conclusion can be utilized with the aim of personalizing drug delivery and designing more accurate clinical trials based on the improved model simulations in order to save cost and time. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8+ T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields. [Display omitted] [ABSTRACT FROM AUTHOR]

Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of in situ recurrence, while AuNRs in the other agent was used for photothermal therapy (PTT), together with anti-PDL1 mediated immunotherapy to alleviate the process of tumor metastasis. A series of assays indicated that this synergistic immunotherapy could induce tumor cell death and the increased generation of CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Besides, more immune factors (IL-2, IL-6, and IFN- γ) produced by synergistic immunotherapy were secreted than mono-immunotherapy. This cooperative immunotherapy strategy could be utilized for diagnosis and treatment of postoperative tumor recurrence at the same time, providing a new perspective for basic and clinical research. This efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. [Display omitted] [ABSTRACT FROM AUTHOR]

Decades of research into the management of cutaneous malignant melanoma have proven it to be a 'tough nut to crack', and its incidence has continued to increase over the last 30 years. Surgery remains a gold standard for early-stage melanoma with five-year survival of 98% for stage I disease, and 90% for stage II. Nonetheless, patients with stage III disease are at a higher risk, resulting in local recurrence as well as distant metastasis. Research regarding the control of metastatic malignant melanoma of the head and neck has evolved. Currently the search is on to understand metastatic malignant melanoma as a heterogeneous disease both at the molecular and clinical level. This paper focuses on the latest systemic therapy for metastatic disease of the head and neck, including cytotoxic chemotherapy, immunotherapy, and target therapy. The new eighth edition of tumour staging, and the sequelae for malignant melanoma, sentinel lymph node biopsy (SLNB), surgical intervention, and its benefits and shortfalls, are discussed. Also, the outcome of our cohort series of patients with metastatic cutaneous malignant melanoma who were treated with systemic combination therapy in Dorset is presented. [ABSTRACT FROM AUTHOR]

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa. The latest findings on the immune checkpoints (ICPs) mediating immunosuppression in tumor microenvironment (TME) are reviewed. Different approaches for targeting ICPs in TME of pancreatic cancer (PCa) and the latest clinical applications are discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Although novel knowledge has been acquired on the molecular landscape of glioblastoma (GBM), a relatively few steps forward have been made regarding its therapy. With the increasing use of novel immunotherapeutic drugs capable of stimulating the antitumor inflammatory response, in the last decades numerous studies aimed to characterize the tumor-associated microenvironment (TME) and its relationship with the immunogenicity of GBM. In this regard, although the tumor-associated microglia and macrophages (TAMs) and PD-L1/PD-1 axis have been emerged as one of the most relevant components of the GBM TME and one of the potential molecular pathways targetable with immunotherapy, respectively. It has been supposed that TAMs may acquire different phenotypes, switching from M1 to M2 phenotypes, with tumor-suppressive and tumor-stimulating role depending on the different surrounding conditions. PD-L1 is a type 1 transmembrane protein ligand expressed by T-cells, B-cells and antigen-presenting cells, with a main inhibitory checkpoint role on tumor immune regulation. While PD-L1 immunohistochemical expression has been extensively investigated in many cancers, its usefulness in the evaluation of GBM response rates to immunotherapy and its standardized evaluation by immunohistochemistry are still debated. The present review paper focuses on the current "state of the art" about the relationship between TME, PD-L1/PD-1 pathway and immunotherapy in GBM, also providing neuropathologists with an updated guide about the clinical trials conducted with PD-L1 and PD-1 inhibitors. [ABSTRACT FROM AUTHOR]

Purpose In this review, we highlight the current concepts and discuss some of the current challenges and future prospects in cancer therapy. We frequently use the example of lung cancer. Methods We conducted a nonsystematic PubMed search, selecting the most comprehensive and relevant research articles, clinical trials, translational papers, and review articles on precision oncology and immuno-oncology. Papers were prioritized and selected based on their originality and potential clinical applicability. Findings Two major revolutions have changed cancer treatment paradigms in the past few years: targeting actionable alterations in oncogene-driven cancers and immuno-oncology. Important challenges are still ongoing in both fields of cancer therapy. On the one hand, druggable genomic alterations are diverse and represent only small subsets of patients in certain tumor types, which limits testing their clinical impact in biomarker-driven clinical trials. Next-generation sequencing technologies are increasingly being implemented for molecular prescreening in clinical research, but issues regarding clinical interpretation of large genomic data make their wide clinical use difficult. Further, dealing with tumor heterogeneity and acquired resistance is probably the main limitation for the success of precision oncology. On the other hand, long-term survival benefits with immune checkpoint inhibitors (anti−programmed death cell protein-1/programmed death cell ligand-1[PD-1/L1] and anti−cytotoxic T lymphocyte antigen-4 monoclonal antibodies) are restricted to a minority of patients, and no predictive markers are yet robustly validated that could help us recognize these subsets and optimize treatment delivery and selection. To achieve long-term survival benefits, drug combinations targeting several molecular alterations or cancer hallmarks might be needed. This will probably be one of the most challenging but promising precision cancer treatment strategies in the future. Implications Targeting single molecular abnormalities or cancer pathways has achieved good clinical responses that have modestly affected survival in some cancers. However, this approach to cancer treatment is still reductionist, and many challenges need to be met to improve treatment outcomes with our patients. [ABSTRACT FROM AUTHOR]

Hepatocellular cancer (HCC) is a common cancer and an important cause of cancer-related death globally. Although surgery is the primary curative treatment, most patients at diagnosis are not surgical candidates and are treated with liver-directed therapy and or systemic therapy. Over the past decade, the systemic treatment options for patients with advanced HCC have evolved. This paper reviews recent progress in systemic therapy and the results of major clinical trials involving novel compounds in patients with HCC. A literature search was performed using keywords related to HCC and systemic therapy. The evidence shows that at the present time an effective adjuvant systemic therapy is not available for patients with early-stage HCC following surgery. In patients with advanced HCC, in addition to sorafenib at least four other targeted agents and several immune checkpoint inhibitors, alone or in combination have been shown to be associated with improved progression-free and overall survival. The optimal sequence of agents, is currently not known, and is determined by patient characteristics, toxicities profile, patients and physicians preference. The future identification of novel active agents and predictive biomarkers are vital to personalize systemic therapy in HCC. [ABSTRACT FROM AUTHOR]

The keys to the prevention of tumor recurrence after operation are the elimination of residual tumor cells and the reversal of microenvironments that induce recurrence. In the formulation of a treatment scheme, building an appropriate drug delivery system is essential. An in-situ drug delivery system (ISDDS) is regarded as an effective treatment route for postoperative use that increases drug delivery efficiency and mitigates side-effects. ISDDS technology has been considerably improved through a clearer understanding of the mechanisms of postoperative recurrence and the development of drug delivery materials. This paper describes the initiation and characteristics of postoperative recurrence mechanisms. Based on this information, design principles for ISDDS are proposed, and a variety of practical drug delivery systems that fulfil specific therapeutic needs are presented. Challenges and future opportunities related to the application of in-situ drug carriers for inhibiting cancer recurrence are also discussed. Unlabelled Image • In-situ drug delivery system (ISDDS) is effective for postoperative drug delivery. • The mechanisms of microenvironment promoting tumor recurrence are summarized. • ISDDSs based on the mechanism of postoperative tumor recurrence • Perspectives of ISDDS for preventing postoperative tumor recurrence [ABSTRACT FROM AUTHOR]

Skin cancers are by far the most common malignancy of humans, particularly in the white population. The growing incidence of cutaneous malignancies has heralded the need for multiple treatment options. Although surgical modalities remain the mainstay of treatment, new research and fresh innovation are still required to reduce morbidity and mortality. Approaches for skin cancer may pass through new technological methods instead of new molecules. The first part of this paper provides a review of the state of the art regarding skin cancer disease as well as epidemiology data. Then, it describes the gold standards of the current recommended therapies worldwide and the actual needs of these patients. This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy. [ABSTRACT FROM AUTHOR]