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Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland). [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a symposium on cell and gene therapy of cancer by the International Society for Cell and Gene Therapy of Cancer is presented. The event was organized by Jim Norris, BSB Medical University of South Carolina, and aided by Katherine Lindley, BSB Medical University of South Carolina. The meeting features reports of highly promising cell-based therapies.

Mucosal melanoma (MM) is a rare and aggressive form of melanoma with a poorer prognosis compared to other subtypes. Recent large-scale next-generation sequencing studies, including our own research, have demonstrated that the molecular characteristics and potential oncogenic drivers of MM differ significantly from those of cutaneous melanoma. The emergence of selective CDK4/6 inhibitors, already approved for use in breast cancer and undergoing phase III clinical trials for other solid tumors, represents a promising development in the treatment of MM. Recent studies have shown that CDK4/6 inhibitors not only induce cell cycle arrest but also play a crucial role in facilitating the interaction between tumor cells and the host immune system. Moreover, our findings indicate that dysregulation of cell cycle progression due to cyclin‐dependent kinase 4 (CDK4) amplification is a significant genetic characteristic in a substantial portion of MM cases. Targeting CDK4 in specific MM patients shows promise for precision cancer therapy, utilizing molecularly characterized MM patient-derived xenograft (PDX) models and clinical trials. This paper provides an overview of existing literature on CDK4/6 dysregulation in MM, as well as preclinical and clinical investigations on CDK4/6 inhibitors and potential combination therapies for MM treatment. [ABSTRACT FROM AUTHOR]

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention. [ABSTRACT FROM AUTHOR]

Superficial tumors are still challenging to overcome due to the high risk and toxicity of surgery and conventional chemotherapy. Microneedles (MNs) are widely used in the treatment of superficial skin tumors (SST) due to the high penetration rate of the stratum corneum (SC), excellent biocompatibility, simple preparation process, high patient compliance, and minimal invasion. Most importantly, MNs can provide not only efficient and rarely painful delivery carriers, but also combine multi-model strategies with photothermal therapy (PTT), immunotherapy, and gene therapy for synergistic efficacy. To promote an in-depth understanding of their superiorities, this paper systematically summarized the latest application progress of MNs in the treatment of SST by delivering various types of photosensitizers, immune signal molecules, genes, and chemotherapy drugs. Just as important, the advantages, limitations, and drug release mechanisms of MNs based on different materials are introduced in the paper. In addition, the application of MN technology to clinical practice is the ultimate goal of all the work. The obstacles and possible difficulties in expanding the production of MNs and achieving clinical transformation are briefly discussed in this paper. To be anticipated, our work will provide new insights into the precise and rarely painful treatment of SST in the future. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 emerged in December 2019 and led to the COVID-19 pandemic. Efforts to develop therapeutics have led to innovations such as mRNA vaccines and oral antivirals. Here we provide a narrative review of the biologic therapeutics used or proposed to treat COVID-19 during the last 3 years. This paper, along with its companion that covers xenobiotics and alternative remedies, is an update to our 2020 paper. Monoclonal antibodies prevent progression to severe disease, are not equally effective across variants, and are associated with minimal and self-limited reactions. Convalescent plasma has side effects like monoclonal antibodies, but with more infusion reactions and less efficacy. Vaccines prevent progression for a larger part of the population. DNA and mRNA vaccines are more effective than protein or inactivated virus vaccines. After mRNA vaccines, young men are more likely to have myocarditis in the subsequent 7 days. After DNA vaccines, those aged 30–50 are very slightly more likely to have thrombotic disease. To all vaccines we discuss, women are slightly more likely to have an anaphylactic reaction than men, but the absolute risk is small. [ABSTRACT FROM AUTHOR]

Background and objective: Due to the suboptimal therapeutic efficacy and potential adverse effects associated with traditional immunosuppressive medications, there has been an increasing emphasis on the development and utilization of immunotherapies. This paper aims to provide clinicians with valuable insights for selecting appropriate therapeutic approaches and contribute to the development of novel immunotherapeutic drugs. Main body: This paper categorizes the immunotherapeutic drugs that are used for the treatment of immune-mediated glomerular diseases into three groups: immunotherapies targeting antigen-presenting cells (anti-CD80), immunotherapies targeting T/B cells (anti-CD20, anti-CD22, BAFF and APRIL inhibitors, CD40-CD40L inhibitors, proteasome inhibitors, Syk inhibitors, and Btk inhibitors), and immunotherapies targeting the complement system (C5 inhibitors, C5a/C5aR inhibitors, C3 inhibitors, MASP2 inhibitors, factor B inhibitors, and factor D inhibitors). The article then provides a comprehensive overview of advances related to these immunotherapeutic drugs in clinical research. Conclusion: Certain immunotherapeutic drugs, such as rituximab, belimumab, and eculizumab, have exhibited notable efficacy in treating specific immune-mediated glomerular diseases, thereby providing novel therapeutic approaches for patients. Nonetheless, the efficacy of numerous immunotherapeutic drugs remains to be substantiated. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the significant diseases that threaten the survival of men worldwide, with the progression of androgen deprivation therapy, become much rely on it, finally, developed into castration-resistant prostate cancer (ADT). In western countries, ranks second in incidence, and in China, with increasing lifespan, the incidence of prostate cancer is rising steadily. Although chemotherapy agents, such as taxane, have achieved some efficacy, treatment failure still occur. As sensitivity of hormone levels change, the disease can progress to castrate-resistant prostate cancer. Because of the poor efficacy of traditional surgery, endocrine therapy, radiation therapy, and chemotherapy, the treatment options for castrate-resistant prostate cancer are limited. Advanced prostate cancer can progress on immunotherapy, and thus, bio -immunotherapy targeting the unique, prostate microenvironment is an important option. In this paper, we systematically revealed the role of three types of bio-immunotherapies (immune checkpoint inhibitors, tumors, vaccines, cytokines) in castrate-resistant prostate cancer, providing a reference for clinical treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose of Review: Decision-making for systemic treatments in older patients with cancer is difficult because of concerns for decreased organ function, risk of toxicity, limited life expectancy due to comorbidities and the lack of evidence available to guide its management in this population. Here, we review the data on the role of systemic agents for the treatment of common malignancies in this age group. Recent Findings: Evidence on the use of systemic treatments for older patients with cancer is increasing, especially for newer options including immune checkpoint inhibitors and targeted agents that provide comparable benefit in older and younger patients. Nonetheless, the risks for short- and long-term toxicities need to be considered. More research is warranted and represents a unique opportunity to increase the knowledge on cancer treatment for older adults. Summary: Healthy, older individuals should be considered for standard systemic treatment options, whereas those at risk based on geriatric assessments require adjusted plans. Geriatric assessments are key for decision-making. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most lethal malignant tumors, characterized by high incidence and poor prognosis. Patients relapse occurred in 65–80% after initial treatment. To date, no effective treatment has been established for these patients. Recently, CD47 has been considered as a promising immunotherapy target. In this paper, we reviewed the biological roles of CD47 in ovarian cancer and summarized the related mechanisms. For most types of cancers, the CD47/Sirpα immune checkpoint has attracted the most attention in immunotherapy. Notably, CD47 monoclonal antibodies and related molecules are promising in the immunotherapy of ovarian cancer, and further research is needed. In the future, new immunotherapy regimens targeting CD47 can be applied to the clinical treatment of ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Donald L. Morton, MD, epitomized one of America's dream scenarios: a person evolving from the humblest of origins to become an international celebrity in his profession, leading the world in the discipline of surgical oncology. His pioneering accomplishments in various roles have been well documented. Scientists, clinicians, students, and patients benefited from his contributions to the management of malignant diseases, particularly melanoma. His many attributes in pursuing the goal to cure malignant diseases are well known. Browsing the scientific literature reveals an almost unmatched publication record and continuous National Institutes of Health funding. He revealed dozens of original concealed ideas, not least of which is the tumor-draining regional lymph node, now called the sentinel lymph node (SLN). When others gave up on the original promise of immunotherapy, he saw the future, the clinical promise which has lately materialized in the control of previously untreatable malignancies. He regarded the fellowship-training of more than 100 surgical oncologists as one of his biggest achievements. In this article, we celebrate the human side of a man with creative courage and far-reaching insight. [ABSTRACT FROM AUTHOR]

The immune system plays a pivotal role in the battle against cancer, serving as a formidable guardian in the ongoing fight against malignant cells. To combat these malignant cells, immunotherapy has emerged as a prevalent approach leveraging antibodies and peptides such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 to inhibit immune checkpoints and activate T lymphocytes. The optimization of gut microbiota plays a significant role in modulating the defense system in the body. This study explores the potential of certain gut-resident bacteria to amplify the impact of immunotherapy. Contemporary antibiotic treatments, which can impair gut flora, may diminish the efficacy of immune checkpoint blockers. Conversely, probiotics or fecal microbiota transplantation can help re-establish intestinal microflora equilibrium. Additionally, the gut microbiome has been implicated in various strategies to counteract immune resistance, thereby enhancing the success of cancer immunotherapy. This paper also acknowledges cutting-edge technologies such as nanotechnology, CAR-T therapy, ACT therapy, and oncolytic viruses in modulating gut microbiota. Thus, an exhaustive review of literature was performed to uncover the elusive link that could potentiate the gut microbiome's role in augmenting the success of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. However, immune-related adverse events (irAEs) and undesired response patterns such as progression after the initial good response in a subset of patients pose a major challenge and drawback to ICIT. This paper provides deep insight into ICIT related bottlenecks and corresponding effective management and combat strategies for very complex complications. Methods: The relevant literatures from PubMed have been reviewed. Based on obtained information, rigorous and exhaustive analyses have been made to present novel methods and strategies against ICIT drawbacks and bottlenecks. Results: The results show that baseline biomarker tests are very crucial to identify suitable candidates for ICIT and frequent assessments throughout ICIT help to recognize possible irAEs at early stages. Equally important are the necessity for mathematical definitions for the ICIT success rate and optimum duration, and the development of combat mechanisms against loss of sensitivity within the tumor microenvironment (TME). Conclusion: Rigorous management approaches are presented for mostly observed irAEs. Furthermore, for the first time in the literature, a non-linear mathematical model is invented to measure the ICIT success rate and to decide about the optimum ICIT duration. Finally, a strategy against tumor plasticity is introduced. [ABSTRACT FROM AUTHOR]

Among the most important sources of β-glucans are edible and medicinal mushrooms. These molecules are components of the cellular wall of basidiomycete fungi (mushrooms) and can be extracted even from the basidiocarp as the mycelium and its cultivation extracts or biomasses. Mushroom β-glucans are recognized by their potential effects as immunostimulants and immunosuppressants. They are highlighted as anticholesterolemic, anti-inflammatory, adjuvant in diabetes mellitus, mycotherapy for cancer treatment, as well as adjuvants for COVID-19 vaccines. Due to their relevance, several techniques of β-glucans extraction, purification, and analysis have already been described. Despite the previous knowledge of β-glucans' benefits for human nutrition and health, the main information about this topic refers to the molecular identification, properties, and benefits, as well as their synthesis and action on cells. Studies on biotechnology industry applications (product development) and the registered products of β-glucans from mushrooms are still limited and more common for feed and healthcare. In this context, this paper reviews the biotechnological production of food products containing β-glucans from basidiomycete fungi, focusing on food enrichment, and presents a new perspective on fungi β-glucans' use as potential immunotherapy agents. Key points: • Mushrooms' β-glucans for product development in the biotechnology industry • Biotechnological production of food products containing mushrooms' β-glucans • Basidiomycete fungi β-glucans are used as potential immunotherapy agents [ABSTRACT FROM AUTHOR]

Recent clinical and pathological evidence has implicated the gut microbiota as an interplay for regulating human body homeostasis, influencing conditions ranging from cancer and dementia to obesity and social behavior. It has the potential to influence cancer prognosis and the results of cancer therapies such as chemotherapy, radiation therapy, and immunotherapy. A growing body of evidence suggests that modulating the gut microbiota can improve the efficacy of anticancer drugs. Nanomedicine has emerged as one of the most promising technologies for modernizing traditional approaches. Accordingly, specific attention has been grabbed toward using nanomaterials to modulate the gut microbiota to enhance the anticancer treatment efficacy. The critical roles of gut microbiota in carcinogenesis, cancer progression, and various cancer therapies are first introduced in this review. Following that, nanomedicine advances that improve cancer therapy efficacy by modulating or engineering gut microbiota are highlighted. Finally, the challenges and opportunities of using nanomedicine to target gut microbiota for cancer prevention and treatment are briefly discussed. Although there are some review papers in this concept, but there are room for further clarification to shed light on the way cross-talk between gut microbiota and cancer and, more specifically, modulating effects and emerging roles of nanomaterials. Nanomaterials crosstalk with gut microbiome [ABSTRACT FROM AUTHOR]

Cancer, the most deadly disease, is known as a recent dilemma worldwide. Presently different treatments are used for curing cancers, especially solid cancers. Because of the immune-enhancing functions of cytokine, IL-21 as a cytokine may have new possibilities to manipulate the immune system in disease conditions, as it stimulates NK and CTL functions and drives IgG antibody production. Indeed, IL-21 has been revealed to elicit antitumor-immune responses in several tumor models. Combining IL-21 with other agents, which target tumor cells, immune-regulatory circuits, or other immune-enhancing molecules enhances this activity. The exciting breakthrough in the results obtained in pre-clinical situations has led to the early outset of present developing clinical trials in cancer patients. In the paper, we have reviewed the function of IL-21 in solid tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Tumor vaccines are a promising approach to activate patient's own immune system to fight against tumor. Traditional tumor vaccines utilize tumor cells or tumor antigens to induce specific anti-tumor immune responses, inhibit tumor growth, and achieve the goal of tumor clearance. However, the currently developed tumor antigens are limited to identifying new antigens and focusing on stimulating or intervening in a designated target, which cannot achieve the cascade effect of tumor immunotherapy and leads to poor treatment outcomes. Therefore, an ideal tumor vaccine should effectively solve the problem of tumor heterogeneity and deliver tumor antigens to lymph nodes, promoting antigen uptake and presentation by antigen-presenting cells to stimulate T cell activation. In recent years, tumor whole-cell vaccines prepared by nanotechnology have emerged as a promising approach to transform the entire tumor into personalized tumor antigens without identifying and separating new antigens. These vaccines can achieve the cascade effect of tumor immunotherapy, effectively activating the patient's own immune system. This paper aims to summarize and review the latest research progress on tumor whole-cell vaccines designed based on nanotechnology. The focus is on targeting key nodes in the process of tumor immunotherapy and gradually initiating these important nodes to achieve the cascade effect of tumor immunotherapy, thereby inhibiting tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each. Ferroptosis in the tumor microenvironment involves intricate crosstalk between tumor cells and immune cells. Through MHC recognition, CD8+T cells activate the JAK1/STAT1 pathway in tumor cells, impairing the function of System Xc and reducing GSH and GPX4 expression to promote tumor cell ferroptosis. Additionally, activation of the STAT1-IRF1-ACSL4 pathway could also promote ferroptosis. The blockade of the antioxidant pathway in tumor cells induces ferroptosis, and the released DAMPs could promote DCs maturation through the cGAMP-STING-TBK1 pathway, leading to antigen presentation that activates CD8+T cells. The release of DAMPs also induces the M1-type polarization of macrophages, which exerts an anti-tumor effect. The anti-tumor effects of CD8+T cells could also be enhanced by blocking inhibitory immune checkpoints such as PD-1, PD-L1, CTLA4, and LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; CTLA4, cytotoxic T lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase 4; GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon regulatory factor 1;IRP1, iron regulatory protein 1; JAK 1, janus kinase; LAG3, lymphocyte activation gene 3; MHC, major histocompatibility complex; NRF2, nuclear factor erythroid-2-related factor 2; PD-1, programmed death protein -1; PD-L1, programmed death ligand 1; PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer and activator of transcription 1; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1 TLR2, toll-like receptor 2. This diagram was drawn by Figdraw (www.figdraw.com). [ABSTRACT FROM AUTHOR]

Immunotherapy improves the prognosis of patients with advanced lung cancer. The expression level of PD-L1 in lung cancer tissue is the most reliable marker for predicting the efficacy of immunotherapy. However, the relationship between PD-L1 expression level and clinicopathological characteristics in patients with lung adenocarcinoma is unclear. The paper aims to analyze the correlation between PD-L1 expression and clinicopathological features in surgically resected lung adenocarcinoma. Clinicopathological data of 100 patients with surgically resected lung adenocarcinoma admitted to the Department of Thoracic Surgery of our hospital from January 2021 to August 2021 were retrospectively analyzed. Immunohistochemistry showed that 36 patients had positive PD-L1 results in postoperative tumor tissues (incidence rate, 36.0%). The tumor-node-metastasis stage, tumor stage, node stage, degree of differentiation, smoking history, and intravascular cancer embolus were statistically different between the two groups (P < 0.05). Multivariate logistic regression analysis showed that postoperative pathological stages above stage II, T3-4, N1-2, poorly differentiated tumors, and positive intravascular cancer embolus were independent factors for PD-L1 positive in lung adenocarcinoma tissue. Therefore, these patients require more attention in the clinic to increase the efficiency of immunotherapy. [ABSTRACT FROM AUTHOR]

High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology. [ABSTRACT FROM AUTHOR]

Background: Liver cancer (LC) is a prevalent malignancy and a leading cause of cancer-related mortality worldwide. Extensive research has been conducted to enhance patient outcomes and develop effective prevention strategies, ranging from molecular mechanisms to clinical interventions. Single-cell sequencing, as a novel bioanalysis technology, has significantly contributed to the understanding of the global cognition and dynamic changes in liver cancer. However, there is a lack of bibliometric analysis in this specific research area. Therefore, the objective of this study is to provide a comprehensive overview of the knowledge structure and research hotspots in the field of single-cell sequencing in liver cancer research through the use of bibliometrics. Method: Publications related to the application of single-cell sequencing technology to liver cancer research as of December 31, 2023, were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace, and R package “bibliometrix” were used to conduct this bibliometric analysis. Results: A total of 331 publications from 34 countries, primarily led by China and the United States, were included in this study. The research focuses on the application of single cell sequencing technology to liver cancer, and the number of related publications has been increasing year by year. The main research institutions involved in this field are Fudan University, Sun Yat-Sen University, and the Chinese Academy of Sciences. Frontiers in Immunology and Nature Communications is the most popular journal in this field, while Cell is the most frequently co-cited journal. These publications are authored by 2799 individuals, with Fan Jia and Zhou Jian having the most published papers, and Llovet Jm being the most frequently co-cited author. The use of single cell sequencing to explore the immune microenvironment of liver cancer, as well as its implications in immunotherapy and chemotherapy, remains the central focus of this field. The emerging research hotspots are characterized by keywords such as 'Gene-Expression', 'Prognosis', 'Tumor Heterogeneity', 'Immunoregulation', and 'Tumor Immune Microenvironment'. Conclusion: This is the first bibliometric study that comprehensively summarizes the research trends and developments on the application of single cell sequencing in liver cancer. The study identifies recent research frontiers and hot directions, providing a valuable reference for researchers exploring the landscape of liver cancer, understanding the composition of the immune microenvironment, and utilizing single-cell sequencing technology to guide and enhance the prognosis of liver cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. Methods: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. Results: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. Conclusion: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature. [ABSTRACT FROM AUTHOR]

Opinion Statement: This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area. [ABSTRACT FROM AUTHOR]

In advanced non-small cell lung cancer (NSCLC), response to immunotherapy is difficult to predict from pre-treatment information. Given the toxicity of immunotherapy and its financial burden on the healthcare system, we set out to identify patients for whom treatment is effective. To this end, we used mutational signatures from DNA mutations in pre-treatment tissue. Single base substitutions, doublet base substitutions, indels, and copy number alteration signatures were analysed in m = 101 patients (the discovery set). We found that tobacco smoking signature (SBS4) and thiopurine chemotherapy exposure-associated signature (SBS87) were linked to durable benefit. Combining both signatures in a machine learning model separated patients with a progression-free survival hazard ratio of 0.40 - 0.17 + 0.28 on the cross-validated discovery set and 0.24 - 0.14 + 0.31 on an independent external validation set ( m = 56 ). This paper demonstrates that the fingerprints of mutagenesis, codified through mutational signatures, select advanced NSCLC patients who may benefit from immunotherapy, thus potentially reducing unnecessary patient burden. [ABSTRACT FROM AUTHOR]

Pituitary tumors are rare neoplasms, with a heterogeneous biological and clinical behavior, due to their clinical course, local invasive growth, resistance to conventional therapies and the risk of disease progression. Recent studies on tumor microenvironment (TME) provided new knowledge on the biology of these neoplasia, that may explain the different phenotypes of these tumors and suggest new biomarkers able to predict the prognosis and the treatment outcome. The identification of molecular markers that act as targets for biological therapies may open new perspectives in the medical treatments of aggressive pituitary tumors. In this paper, we will review data of TME and target therapies in somatotropinomas. [ABSTRACT FROM AUTHOR]

Introduction: Cancer immunotherapy represents one of the most important innovations in modern medicine. Durvalumab is an anti-programmed cell death ligand 1 (PDL-1) agent which is currently under investigation in several studies in combination with the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drug tremelimumab. The aim of this review was to systematically identify and revise the current scientific literature investigating the combination of these two drugs in solid tumors. Methods: A digital search on the Medline (PubMed interface) and Scopus databases for articles published from inception to 26 February 2021 was performed. The terms used for the search were durvalumab AND tremelimumab. Trials reported in English involving adult patients with solid cancers treated with the combination durvalumab plus tremelimumab were retrieved; the references of the articles were cross-checked to identify missing papers. Results: The electronic search produced 267 results; after exclusion of duplicates, irrelevant articles, reviews, and papers not in English or missing data, 19 articles were included for revision. The total number of patients treated with the combination of durvalumab and tremelimumab in the studies retrieved was 2052. Conclusion: The combination of durvalumab plus tremelimumab showed some oncological advantages in comparison with traditional chemotherapies in some subsets of tumors, but generally has not shown consistent advantages in comparison with the employment of durvalumab monotherapy. A number of the studies examined had intrinsic methodological limitations; therefore, future well-designed studies involving larger cohorts are warranted. [ABSTRACT FROM AUTHOR]

Background: Over the last decade, since clinical trials examining targeted therapeutics for gliomas have failed to demonstrate a meaningful increase in survival, the emphasis has recently been switched toward innovative techniques for modulating the immune response against tumors and their microenvironments (TME). Cancerous cells have eleven hallmarks which make it distinct from normal ones, among which is immune evasion. Immune evasion in glioblastoma helps it evade various treatment modalities. Summary: Glioblastoma's TME is composed of various array of cellular actors, ranging from peripherally derived immune cells to a variety of organ-resident specialized cell types. For example, the blood–brain barrier (BBB) serves as a selective barrier between the systemic circulation and the brain, which effectively separates it from other tissues. It is capable of blocking around 98% of molecules that transport different medications to the target tumor. Objectives: The purpose of this paper is to offer a concise overview of fundamental immunology and how 'clever' gliomas avoid the immune system despite the discovery of immunotherapy for glioma. Conclusions: Herein, we highlight the complex interplay of the tumor, the TME, and the nearby normal structures makes it difficult to grasp how to approach the tumor itself. Numerous researchers have found that the brain TME is a critical regulator of glioma growth and treatment efficacy. [ABSTRACT FROM AUTHOR]

Regarding the increasing prevalence of cancer throughout the globe, the development of novel alternatives for conventional therapies is inevitable to circumvent limitations such as low efficacy, complications, and high cost. Recently, microneedle arrays (MNs) have been introduced as a novel, minimally invasive, and low-cost approach. MNs can delivery both small molecule and macromolecular drugs or even nanoparticles (NPs) to the tumor tissue in a safe and controlled manner. Relying on the recent promising outcomes of MNs in transdermal delivery of anticancer agents, this review is aimed to summarize constituent materials, fabrication methods, advantages, and limitations of different types of MNs used in cancer therapy applications. This review paper also presents the potential use of MNs in transdermal delivery of NPs for effective chemotherapy, gene therapy, immunotherapy, photodynamic, and photothermal therapy. Additionally, MNs are currently explored as routine point-of-care health monitoring devices for transdermal detection of cancer biomarkers or physiologically relevant analytes which will be addressed in this paper. Despite the promising potential of MNs for cancer therapy and diagnosis, several limitations have impeded their therapeutic efficacy and real-time applicability that are addressed in this paper. [ABSTRACT FROM AUTHOR]

Macrophage receptor with collagen structure (MARCO) is a member of scavenger receptor class A (SR-A) and shares structural and functional similarities with SR-A1. In recent years, many studies have shown that MARCO can trigger an immune response and has therapeutic potential as a target for immunotherapy. Studies have shown that alterations in MARCO expression following pathogen infection cause changes in the functions of innate and adaptive immune cells, including macrophages, dendritic cells, B cells, and T cells, affecting the body's immune response to invading pathogens; thus, MARCO plays a crucial role in triggering the immune response, bridging innate and adaptive immunity, and eliminating pathogens. This paper is a comprehensive summary of the recent research on MARCO. This review focuses on the multiple functions of MARCO, including adhesion, migration, phagocytosis, and cytokine secretion with special emphasis on the complex interactions between MARCO and various types of cells involved in the immune response, as well as possible immune-related mechanisms. In summary, in this review, we discuss the structure and function of MARCO and its role in the immune response and highlight the therapeutic potential of MARCO as a target for immunotherapy. We hope that this review provides a theoretical basis for future research on MARCO. [ABSTRACT FROM AUTHOR]

Purpose: Treatment strategies of lymphoid malignancies have been revolutionized by immunotherapy. Because of the inherent property of Hodgkin lymphoma and some subtypes of non-Hodgkin lymphoma as a highly FDG-avid tumor, functional 18F-FDG PET/CT imaging is already embedded in their routine care. Nevertheless, the question is whether it is still valuable in the context of these tumors being treated with immunotherapy. Herein, we will review the value of 18F-FDG PET/CT imaging lymphoid tumors treated with immunotherapy regimens. Methods: A comprehensive literature search of the PubMed database was conducted on the value of the 18F-FDG PET/CT for immunotherapy response monitoring of patients with malignant lymphoma. The articles were considered eligible if they met all of the following inclusion criteria: (a) clinical studies on patients with different types of malignant lymphoma, (b) treatment with anti-CD20 antibodies, immune checkpoint inhibitors or immune cell therapies, (c) and incorporated PET/CT with 18F-FDG as the PET tracer. Results: From the initial 1488 papers identified, 91 were ultimately included in our study. In anti-CD20 therapy, the highest pooled hazard ratios (HRs) of baseline, early, and late response monitoring parameters for progression-free survival (PFS) belong to metabolic tumor volume (MTV) (3.19 (95%CI: 2.36–4.30)), maximum standardized uptake value (SUVmax) (3.25 (95%CI: 2.08–5.08)), and Deauville score (DS) (3.73 (95%CI: 2.50–5.56)), respectively. These measurements for overall survival (OS) were MTV (4.39 (95%CI: 2.71–7.08)), DS (3.23 (95%CI: 1.87–5.58)), and DS (3.64 (95%CI: 1.40–9.43)), respectively. Early and late 18F-FDG PET/CT response assessment in immune checkpoint inhibitors (ICI) and immune cell therapy might be an effective tool for prediction of clinical outcome. Conclusion: For anti-CD20 therapy of lymphoma, the MTV as a baseline 18F-FDG PET/CT-derived parameter has the highest HRs for PFS and OS. The DS as visual criteria in early and late response assessment has higher HRs for PFS and OS compared to the international harmonization project (IHP) visual criteria in anti-CD20 therapy. Early changes in 18F-FDG PET parameters may be predictive of response to ICIs and cell therapy in lymphoma patients. [ABSTRACT FROM AUTHOR]

Purpose: Infiltrating into the vital structure of the brain, located in the inaccessible anatomical region, and having molecular heterogeneity, glioblastoma (GBM) –with no doubt– is one of the deadliest cancers. Using the blood and brain barrier (BBB), GBM makes a shield to restrict the reach of chemotherapeutic agents to the tumor site and evolves a unique microenvironment to furnish all the essentials for cancer cells survival to conceal neoplastic cells from immunosurveillance. Methods: 99 papers which met the criteria of eligibility were included in this review by consensus. The included articles were classified based on their design and level of evidence. Results: Given this characteristic, immunotherapies for a while enjoyed unprecedented attention as a solution for GBM treatment; however, it did not take long before the enthusiasm for their application was muted. It became apparent that cancer cells intelligently find a way to manipulate the anti-tumor responses of agents by attracting immunosuppressive lymphocytes into the brain using the lymphatic vessels. This event makes GBM a good model for immunotherapy resistance. However, the presence of lymphatic vessels has fired up an idea of the adoptive attraction of effector T lymphocytes to the tumor milieu. This was when engineering and cloning technologies, which have given life to one of the recent treatment strategies using artificial T cells named chimeric antigen receptors (CAR) T-cells, came to action to design specific CAR T-cells for the treatment of GBM. Conclusion: The present review summarizes the recent advances in CAR T-cell-based treatments in GBM and discusses why this approach could be positioned as a pillar of the next-generation of immunotherapies for this type of brain tumor. [ABSTRACT FROM AUTHOR]

The article presents papers selected from presentations at the 4th Progress in Vaccincation Against Cancer (PIVAC) conference held in Freudenstadt-Lauterbad, Black Forest, Germany on September 22-25, 2004. It includes a paper on the use of peptide-pulsed autologous dendritic cells in therapeutic cancer vaccination using synthetic peptides. Next is a paper that describes pre-clinical data on the use of modified whole-cell vaccines rather than defined antigens. Suggested advantages of adoptive as opposed to active immunotherapy are given in another paper.

Opinion statement: The primary objective of this study is to evaluate the effectiveness of cancer vaccines containing genetically modified dendritic cells (DCs) in inducing transformational immune responses. This paper sheds considerable light on DCs' function in advancing treatment techniques. This objective is achieved by thoroughly analyzing the many facets of DCs and their strategic integration into cancer treatment. Due to their role as immune response regulators, DCs can potentially enhance cancer treatment strategies. DCs have the potential to revolutionize immunotherapy, as shown by a comprehensive analysis of their numerous characteristics. The review deftly transitions from examining the fundamentals of preclinical research to delving into the complexities of clinical implementation while acknowledging the inherent challenges in translating DC vaccine concepts into tangible progress. The analysis also emphasizes the potential synergistic outcomes that can be achieved by combining DC vaccines with established pharmaceuticals, thereby emphasizing the importance of employing a holistic approach to enhance treatment efficacy. Despite the existence of transformative opportunities, advancement is hindered by several obstacles. The exhaustive analysis of technical complexities, regulatory dynamics, and upcoming challenges provides valuable insights for overcoming obstacles requiring strategic navigation to incorporate DC vaccines successfully. This document provides a comprehensive analysis of the developments in DC-based immunotherapy, concentrating on its potential to transform cancer therapy radically. [ABSTRACT FROM AUTHOR]

Certain innovative technologies applied to medical product development require novel evaluation approaches and/or regulations. Horizon scanning for such technologies will help regulators prepare, allowing earlier access to the product for patients and an improved benefit/risk ratio. This study investigates whether citation network analysis and text mining of scientific papers could be a tool for horizon scanning in the field of immunology, which has developed over a long period, and attempts to grasp the latest research trends. As the result of the analysis, the academic landscape of the immunology field was identified by classifying 90,450 papers (obtained from PubMED) containing the keyword "immune* and t lymph*" into 38 clusters. The clustering was indicative of the research landscape of the immunology field. To confirm this, immune checkpoint inhibitors were used as a retrospective test topic of therapeutics with new mechanisms of action. Retrospective clustering around immune checkpoint inhibitors was found, supporting this approach. The analysis of the research trends over the last 3 to 5 years in this field revealed several candidate topics, including ARID1A gene mutation, CD300e, and tissue resident memory T cells, which shows notable progress and should be monitored for future possible product development. Our results have demonstrated the possibility that citation network analysis and text mining of scientific papers can be a useful objective tool for horizon scanning of life science fields such as immunology. [ABSTRACT FROM AUTHOR]

Purpose of Review: The goal of this paper is to provide a review on the current emerging management strategies as described in the literature pertaining to breast cancer and central nervous system metastases. As systemic oncology treatments evolve, so are new approaches to the management of central nervous system metastases from breast cancer. Recent Findings: In this review, we describe how novel treatment strategies have evolved from standard chemotherapy to more targeted approaches, innovative drug delivery methodologies, immunotherapeutics, and radiotherapeutic approaches. Summary: We describe innovative treatment strategies on the horizon for breast cancer and central nervous metastases. Future therapeutics may be better able to penetrate through the blood–brain-barrier bypassing limitations from standard therapies. These pioneering strategies will hopefully improve patients' quality of life as well as survival. [ABSTRACT FROM AUTHOR]

Currently, nanoscale materials and scaffolds carrying antitumor agents to the tumor target site are practical approaches for cancer treatment. Immunotherapy is a modern approach to cancer treatment in which the body's immune system adjusts to deal with cancer cells. Immuno-engineering is a new branch of regenerative medicine-based therapies that uses engineering principles by using biological tools to stimulate the immune system. Therefore, this branch's final aim is to regulate distribution, release, and simultaneous placement of several immune factors at the tumor site, so then upgrade the current treatment methods and subsequently improve the immune system's handling. In this paper, recent research and prospects of nanotechnology-based cancer immunotherapy have been presented and discussed. Furthermore, different encouraging nanotechnology-based plans for targeting various innate and adaptive immune systems will also be discussed. Due to novel views in nanotechnology strategies, this field can address some biological obstacles, although studies are ongoing. [ABSTRACT FROM AUTHOR]

Purpose: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC.Methods: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic.Results: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response?Conclusion: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited. [ABSTRACT FROM AUTHOR]

Autoimmune diseases—where the immune system mistakenly targets self-tissue—remain hindered by non-specific therapies. For example, even molecularly specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (TREG) that selectively stop attack of host tissue. Much has been done to increase the efficiency of signal delivery using biomaterials, including encapsulation in polymer microparticles (MPs) to allow for co-delivery and cargo protection. However, less research has compared particles encapsulating drugs that target different TREG inducing pathways. In this paper, we use poly (lactic-co-glycolide) (PLGA) to co-encapsulate type 1 diabetes (T1D)-relevant antigen and 3 distinct TREG-inducing molecules — rapamycin (Rapa), all-trans retinoic acid (atRA), and butyrate (Buty) — that target the mechanistic target of Rapa (mTOR), the retinoid pathway, and histone deacetylase (HDAC) inhibition, respectively. We show all formulations are effectively taken up by antigen presenting cells (APCs) and that antigen-containing formulations are able to induce proliferation in antigen-specific T cells. Further, atRA and Rapa MP formulations co-loaded with antigen decrease APC activation levels, induce TREG differentiation, and reduce inflammatory cytokines in pancreatic-reactive T cells. [ABSTRACT FROM AUTHOR]

Second-line treatment options for patients with relapsed, extensive-stage small cell lung cancer (ES-SCLC) are limited, and even with currently available treatments, prognosis remains poor. Until recently, topotecan (a topoisomerase I inhibitor) was the only drug approved by the United States (US) Food and Drug Administration (FDA) for the management of ES-SCLC following progression after first-line treatment with etoposide plus a platinum derivative (EP; carboplatin preferred). With the most recent approval of EP plus a programmed death ligand 1 (PD-L1) inhibitor, there are now more therapeutic options for managing ES-SCLC. A number of novel agents have emerging data for activity in relapsed ES-SCLC, and single-agent lurbinectedin (an alkylating drug and selective inhibitor of oncogenic transcription and DNA repair machinery in tumor cells) has conditional FDA approval for use in this patient population. Trilaciclib, a short-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, has also been recently approved as a supportive intervention for use prior to an EP or a topotecan-containing regimen to diminish the incidence of chemotherapy-induced myelosuppression. The current review is based on a recent expert roundtable discussion and summarizes current therapeutic agents and emerging data on newer agents and biomarkers. It also provides evidence-based clinical considerations and a treatment decision tool for oncologists treating patients with relapsed ES-SCLC. This paper discusses the importance of various factors to consider when selecting a second-line treatment option, including prior first-line treatment, available second-line treatment options, tumor platinum sensitivity, and patient characteristics (such as performance status, comorbidities, and patient-expressed and perceived values). [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have become a hotspot in biomedical research. This interest reflects their extensive involvement in the regulation of the expression of other genes, and their influence on the occurrence and development of a variety of human diseases. Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1) is a recently discovered oncogenic lncRNA. It is highly expressed in a variety of solid tumors, and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs, or by the direct binding to other proteins. Ultimately, AFAP1-AS1 promotes proliferation, chemotherapy resistance, and resistance to apoptosis, maintains stemness, and enhances invasion and migration of tumor cells. This paper summarizes the research concerning AFAP1-AS1 in malignant tumors, including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors. We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research. AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to introduce a novel in silico platform for simulating early-stage solid tumor growth and anti-tumor immune response. We present the model, test the sensitivity and robustness of its parameters, and calibrate it with clinical data from exercise oncology experiments which offer a natural biological backdrop for modulation of anti-tumor immune response. We then perform two virtual experiments with the model that demonstrate its usefulness in guiding pre-clinical and clinical studies of immunotherapy. The first virtual experiment describes the intricate dynamics in the tumor microenvironment between the tumor and the infiltrating immune cells. Such dynamics is difficult to probe during a pre-clinical study as it requires significant redundancy in lab animals and is prohibitively time-consuming and labor-intensive. The result is a series of spatiotemporal snapshots of the tumor and its microenvironment that can serve as a platform to test mechanistic hypotheses on the role and dynamics of different immune cells in anti-tumor immune response. The second virtual experiment shows how dosage and/or frequency of immunotherapy drugs can be optimized based on the aerobic fitness of the patient, so that possible adverse side effects of the treatment can be minimized. [ABSTRACT FROM AUTHOR]

V-domain Ig suppressor of T cell activation (VISTA) is a transmembrane protein that plays a crucial role in the regulation of antitumor immunity. Therapeutic intervention that inhibits the VISTA pathway constitutes a new approach in the treatment of cancer. The aim of the present study was to provide a bibliometric literature review of VISTA research in the field of cancer. Published articles on the topic were retrieved from the Web of Science Core Collection Database of Hassan II University from the beginning of the database to November 14, 2019. The articles were analyzed and a lot of information was available on the Web of Science, such as the number of citations, the names of the authors, country, publication year, Web of Science categories, and journal. A total of 76 papers (research and review articles) were retrieved from the Web of Science Core Collection Database to introduce VISTA research in cancer topic. All of the articles were published in English during the period between 2011 and 2019; the annual publications number has increased from 1 in 2011 to 22 in 2019. Cancer immunology immunotherapy journal, Cancer immunology research journal, and Cancer research journal, each one has published 3 articles (3.9% of the total publications), the impact factors of the journals ranged from 2.34 to 10.19. The author who has published high number of articles was Noelle RJ with 11 articles; according to the keyword co-occurrence, VISTA was the most frequent keyword with a frequency of 42.1%, followed by immune (36.8%). This is the first work that treats the application of bibliometric methods in VISTA research in the oncology field and represents an important bibliographic source for future studies on the role of VISTA in cancer and immunotherapy of cancer. [ABSTRACT FROM AUTHOR]

Purpose of Review: Intravesical BCG therapy (ivBCG) is a treatment for bladder cancer that complements surgery and prevents tumor progression. Reactive arthritis (ReA) is a rare osteoarticular manifestation that can complicate this treatment. An updated systematic literature review has been investigated to identify clinical, biological, and therapeutic data of this pathology. Recent Findings: A systematic literature was performed on October 2020 to identify papers published from 2000 to 2020. Study eligibility criteria included case reports, case series, cohort studies, systematic reviews, meta-analysis, and letters to the editor, in English and French. Independent extraction of articles was performed by two investigators. Thirteen studies met the search criteria for the systematic review with a good quality assessment. The total number of patients was 107, with an average age of 61.5 [24–80]. The symptoms of ReA appeared after a mean number of 5.71 instillations and 13.9 days. Arthritis was the most common symptom (98.13%) followed by fever (80.76%) and conjunctivitis (64.42%). Human leukocyte antigen (HLAB27) was positive in 28.97% of patients. Therapeutic modalities included non-steroidal anti-inflammatory drugs (NSAIDs) (51.4%), corticosteroids (27.1%), conventional synthetic disease-modifying antirheumatic drugs (3.84%), antitubercular drugs (14.42%), and tocilizumab (0.93%). BCG therapy was discontinued in 29.9% of patients. Remission was achieved in 92.3% of patients and one patient progressed to spondyloarthritis. Summary: ReA is a rare complication of BCG therapy. Clinical signs are similar to those of typical ReA and treatment is primarily based on NSAIDs and corticosteroids. [ABSTRACT FROM AUTHOR]

Purpose: Patients harboring high-grade non-muscle-invasive bladder cancer (NMIBC) experience high rates of both recurrence and progression. Currently, few treatment options besides cystectomy exist for this at-risk population, especially those with BCG-unresponsive disease. The purpose of this review is to present the current status and describe future directions of immunotherapy in NMIBC. Methods: The PubMed and Google Scholar databases were searched for articles pertaining to immunotherapy in NMIBC. Relevant planned and ongoing clinical trials were identified using www.ClinicalTrials.gov. Published randomized control trials, reviews, other retrospective and prospective studies deemed relevant were used in this review paper. Results: Novel immunotherapies used in the treatment of high-grade NMIBC and BCG-unresponsive disease allow patients more options and have the potential to reduce the need for radical cystectomy. Currently, several options target the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis as this mechanism of immunotherapy has been shown to be effective in several cancers, including bladder, melanoma, and lung cancers. In addition, other immunotherapy options for the treatment of NMIBC include viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines. Conclusions: The current landscape of immunotherapy in bladder cancer is rapidly evolving, with much literature pertaining to muscle-invasive and metastatic disease. However, the implementation of these treatment options in high-grade NMIBC may allow patients to avoid life-altering surgery. Reliable biomarkers for response are needed to further select patients who may benefit from such therapies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development. Results: Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients. Even in therapy, the small radioactively labeled nanobodies prove to be superior to radioactively labeled monoclonal antibodies due to their higher specificity and their ability to penetrate the tumor. Conclusion: While monoclonal antibodies are well established drug delivery vehicles, the current literature on molecular imaging supports the notion that antibody fragments, such as affibodies or nanobodies, might be superior in this approach. [ABSTRACT FROM AUTHOR]

This paper chronicles the third decade of MASCC from 2010. There was a generational change in this decade, building on the solid foundation of the founders. It included the first female President, and a new Executive Director with a background in strategy and business development and operations as applied to healthcare. The headquarters moved from Copenhagen to Toronto. The first meeting to be held outside of Europe or North America was held in Adelaide, Australia, and the membership in the Asia Pacific region expanded. A program of international affiliates saw national supportive care organisations formally link with MASCC. In cancer supportive care, there was a raft of new toxicities to manage as immunotherapies were added to conventional cytotoxic treatment. There was also a greater emphasis on the psychosocial needs of patients and families. New MASCC groups were formed to respond to this evolution in cancer management. The MASCC journal, Supportive Care in Cancer, continued to grow in impact, and MASCC published two editions of a textbook of supportive care and survivorship. The decade ended with the challenge of the COVID-19 pandemic, but that served to highlight the importance of good supportive care to patients with cancer. [ABSTRACT FROM AUTHOR]

Pembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL. Overall results indicate that CL decreases over the treatment period of a typical patient in a pattern well described by a sigmoidal function of time with three parameters: the maximum proportion change in CL from baseline (approximately I or exactly e − 1), the time to reach I/2 (TI), and a Hill coefficient. Best overall response per response evaluation criteria in solid tumor category was found to be associated with the magnitude of I. [ABSTRACT FROM AUTHOR]

Purpose of Review: This paper aims to summarize the data of recently completed and key ongoing clinical trials of systemic agents for advanced hepatocellular carcinoma (aHCC). In particular, the review focuses on ongoing checkpoint inhibitor combination trials and promising studies combining tyrosine kinase inhibitors with checkpoint inhibitors. Recent Findings: The recently approved combination of atezolizumab and bevacizumab based on the IMbrave150 trial has shown the most potential with the highest overall survival of any systemic agent in HCC to date, surpassing sorafenib. Despite COVID-19 delays, other promising trials that involve combining VEGF-directed therapy and checkpoint inhibition, cancer vaccines, phosphatidylserine, YIV-906, and oncolytic and immunotherapeutic vaccinia virus are actively recruiting patients. Summary: After almost a 10-year dormancy, the list of potential systemic treatment options for aHCC is growing rapidly. Given the promising data from the IMbrave150 trial, the combination of atezolizumab and bevacizumab is now the new first-line therapy. We discuss the change in landscape, the new second- and third-line systemic treatments in aHCC, and the ongoing clinical trials for newer agents including combination therapies. [ABSTRACT FROM AUTHOR]

Summary: In oncology clinical research, the analysis and reporting of adverse events is of major interest. A consistent depiction of the safety profile of a new treatment is as crucial in establishing how to use it as its antitumor activity. The advent of new therapeutics has led to major changes in the management of patients and targeted therapies or immune checkpoint inhibitors are administered continuously for months or even years. However, the classical methods of adverse events analysis are no longer adequate to properly assess their safety profile. Indeed, the worst grade method and time-to-event analysis cannot capture the duration or the evolution of adverse events induced by extended treatment durations. Many authors have highlighted this issue and argue that the analysis of safety data from clinical trials should be modernized by considering the dimension of time and the recurrent nature of adverse events. This paper aims to illustrate the limitations of current methods and discusses the value of alternative approaches such as the prevalence function, Q-TWiST, the ToxT and the recurrent event approaches. The rationale and design of the MOTIVATE trial, which aims to model the evolution of toxicities over time using the prevalence function in patients treated by immunotherapy, is also presented (ClinicalTrials.gov Identifier: NCT03447483; Date of registration: 27 February 2018). [ABSTRACT FROM AUTHOR]