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Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer, as the second leading cause of death worldwide, has become an ongoing public health challenge and its treatment has received much attention, with immunotherapy becoming a hot research topic in recent years. The interferon gene stimulating factor (STING)-mediated signaling pathway has a "double-edged sword" role in cancer, which plays different roles in different types and stages of tumors. In this paper, we discuss the current research status, cooperation, and hotspots of STING signaling pathway in cancer from 2008–2022 using CiteSpace software based on the literature of cancer and STING signaling pathway. In addition, we predicted future research trends in this field by analysis, and the results showed that the STING signaling pathway is rapidly increasing in cancer research, and its role in tumor microenvironment and immunotherapy has become a new hot spot in current research and will continue to receive high attention. [ABSTRACT FROM AUTHOR]

Immunohistochemical staining is a common technique to study tissue morphology and in situ protein expression. With the rise of immunotherapy, more and more markers in the tumor microenvironment have been discovered. In this paper, the multiplex immunofluorescence staining method was used to stain paraffin sections of 35 cases of gastric adenocarcinoma tissue and 35 cases of colorectal adenocarcinoma tissue and its adjacent tissue. The infiltration of CD8+ T cells and CD103+CD8+ T cells in the slices was detected by using the slice scanner to form the map and CaseViewer2.0 software analysis. The experimental results in this paper showed that compared with adjacent tissues, the infiltration degree of CD8+ T cells in gastric adenocarcinoma tissue was significantly lower (Z = 2.244 , P = 0.025 , P < 0.05), and the infiltration degree of cells was significantly lower (Z = 2.785 , P = 0.005 , P < 0.05). In gastric adenocarcinoma tissue, the infiltration of CD8+ T cells was correlated with the tumor diameter of gastric adenocarcinoma (P = 0.002). There was a statistically significant difference. The degree of CD103+CD8+ T cell infiltration was related to the survival of patients with gastric adenocarcinoma (P = 0.002) and the degree of tumor differentiation (P = 0.004). The infiltration of CD103+CD8+ T cells in gastric cancer tissue and colorectal cancer tissue is related to the survival of patients. CD103+CD8+ T cells are thought to play a role in the prognosis of gastric adenocarcinoma and colorectal adenocarcinoma. Experiments have shown that the more the CD103+CD8+ T cells, the better the prognosis of gastric adenocarcinoma and colorectal adenocarcinoma, so the prognosis of gastric adenocarcinoma and colorectal adenocarcinoma can be improved by increasing CD103+CD8+ T cells. [ABSTRACT FROM AUTHOR]

In recent years, many studies have focused on the host immune system and its relationship with tumor progression in a variety of solid tumors, including breast cancer. This study investigates recent trends of immunotherapy research in breast cancer and compares the contributions of research from different regions, institutions, and authors. A search of breast cancer and immunotherapy studies that were published between 2010 and 2019—with different keyword combinations—was performed in the Web of Science database. Bibliometric data were collected for analysis. VOSviewer software was used to generate a figure for the keyword's co-occurrence network, so as to implement network visualization analysis. A total of 1,041 publications were identified. The United States and China contributed to approximately 50% of the publications, 336 and 208, respectively. Both countries drove the increase in publications after 2015. A paper entitled "Pembrolizumab in patients with advanced triple-negative breast cancer: Phase IB KEYNOTE-012 Study" that was published in the Journal of Clinical Oncology by Nanda et al. was the most cited (715 citations). The keywords found in this research were grouped into four clusters: "mechanism," "vaccination," "PD-L1," and "chemotherapy." The terms "tumor-infiltrating lymphocytes" and "PD-1/PD-L1" are among the latest hotspots, which mostly appeared in 2017. Author keyword analysis revealed that recent trends in breast cancer immunotherapy focus on the triple-negative breast cancer subtype and PD-1/PD-L1 immune checkpoint pathway and inhibitors. This study analyzed global trends in immunotherapy research on breast cancer over the past 10 years and provided insight into the features and research hotspots of the articles in this issue. [ABSTRACT FROM AUTHOR]

Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts. [ABSTRACT FROM AUTHOR]

Objective: To analyze the therapeutic effects and organ rejection of anti-PD-1 immunotherapy or antivascular targeting therapy on patients with combined malignancies after organ transplantation.Methods: We collected retrospective studies on "post-transplantation, cancer, immunotherapy, and vascular targeting therapy" in Embase, Wanfang database, Cochrane Library, VIP databases, CNKI, and PubMed, and the case data were organized and analyzed.Results: Data from only 40 papers met our requirements, which included 2 literature reviews, 4 original researches, and 34 case reports from 2016 to 2020. A total of 40 studies involving 66 patients were included, who were divided into 3 groups (patients using CTLA-4 inhibitors, group 1; patients who received sequential or concurrent anti-PD-1 and anti-CTLA-4 therapy, group 2; and patients using PD-1/PD-L1 inhibitors, group 3). There was no statistical difference in patients' DCR between the three groups (P > 0.05). Also, compared with group 2, there was no statistically significant difference in recipient organ rejection in group 1 and group 3 (P > 0.05). The DCR rate for antivascular targeted therapy is approximately 60%.Conclusions: Immunotherapy should be carefully selected for patients with combined malignancies after organ transplantation. Antivascular targeted therapy is one of the options worth considering; the risk of side effects of drug therapy is something that needs to be closely monitored when combined with immunotherapy. [ABSTRACT FROM AUTHOR]

Malignant melanoma is one of the most threatening cancers to human health. Only 14% of patients with malignant melanoma have a remaining life span of 5 years. At present, there have been some studies looking for potential prognostic indicators of esophageal cancer from the level of genes and infiltrating immune cells, but there are still some problems that need to be resolved urgently. This paper proposes IGHG3 as the immune infiltration of malignant melanoma, which takes into account the computational mathematics. It aims to deduce the characteristics of immune cell infiltration in malignant melanoma and study the relationship between different immune cell infiltration characteristics and prognosis. The method in this article is to establish a computational mathematical model for the immunotherapy of melanoma, then study the method of identification of the affinity of the IGHG3 reagent, and finally obtain the gene expression of immune infiltration. The functions of these methods are, respectively, to predict the dynamic behavior of T cells with two different specificities through mathematical models and to test the matching degree of different concentrations of IGHG3 reagent with the human body. Then use the ssGSEA algorithm to obtain immune infiltration related data and calculate the difference between the weighted empirical cumulative distribution function of all genes in the effect of IGHG3 on melanoma that was carried out. The experimental results showed the computational mathematical method genome and all the remaining genes. In this study, a computational mathematical method to detect the IGHG3 gene expression had a significant inhibitory effect on A375 cells in the experimental group, and the knockdown efficiency reached 85.6%. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy brings substantial and long-term clinical benefits that can even cure tumors. However, the accumulation of evidence suggests that immunotherapy also induces severe and complex neurologic immune-related adverse events (ir-AEs) and even leads to immunotherapy-related death, which arouses the concern of clinicians. The timely and accurate identification of neurotoxicity helps clinicians detect and treat these complications early, thereby enhancing treatment efficiency and improving the prognosis of patients. At present, the mechanism of neurotoxicity caused by immunotherapy has not been completely elucidated. This paper mainly reviews the clinical features, pathogenesis, and therapeutic strategies of neurologic ir-AEs. [ABSTRACT FROM AUTHOR]

Tumor is the most serious threat to human beings. Although war against cancer has been launched over forty years, cancer treatment is still far away from being satisfactory. Immunotherapy, especially checkpoint blockade immunotherapy, is a rising star that shows a promising future. To fulfill the requirement of depleting primary tumor and inhibiting tumor metastasis and recurrence, many researchers combined checkpoint blockade immunotherapy with other treatment strategies to extend the treatment outcome. Photodynamic therapy could induce immunogenic cell death, and checkpoint blockade could further accelerate the immunity; therefore, combining these two strategies publishes many papers. Additionally, photothermal therapy and immunotherapy were also utilized for combining with checkpoint blockade, which were also reviewed in this paper. Furthermore, antibodies, siRNA, and small molecule inhibitors are developed to block the checkpoint; therefore, we categorized the papers into three sections, combination nanoparticles with checkpoint blockade antibody, combination nanoparticles with checkpoint blockade siRNA, and combination nanoparticles with small molecule checkpoint inhibitors, and related researches were summarized. In conclusion, the combination nanoparticle with checkpoint blockade cancer immunity is a promising direction that may fulfill the requirement of cancer treatment. [ABSTRACT FROM AUTHOR]

As a reproductive endocrine disease, polycystic ovary syndrome (PCOS) has influenced billions of women during childbearing age worldwide. Owing to its complex etiology and ambiguous pathogenesis, there is still not a specific method to cure it. Clinical treatments, such as hormone therapy and surgical treatment, have side effects. Therefore, it is essential and urgent to seek alternative treatment to solve these problems. The satisfactory efficacy of complementary and alternative medicine (CAM), such as traditional Chinese medicine (TCM), immunotherapy, medicinal foods, vitamin therapy, diet therapy, psychotherapy, spa, and oxygen therapy, in treating PCOS, has aroused an increasing number of medical workers' concern and gradually become the mainstream. This paper reviews the application of CAM in the treatment of PCOS, especially from the perspective of TCM. Meanwhile, the limitations of the literature about CAM in the treatment of PCOS are mentioned and analyzed as well. [ABSTRACT FROM AUTHOR]

Every year, a large number of people fall prey to cancer worldwide and more than half lose their battle to cancer. Among the multimodalities of cancer management, including surgery, hormonal therapy, radiotherapy, and chemotherapy, immunotherapy has revolutionized the treatment of cancer. Cancer immunotherapy, which is occasionally referred to as immune-oncology, induces the patient's own immune system and attempts to exploit the exquisite power and specificity of the immune system for cancer patient treatment. [Extracted from the article]

Objectives. This study aimed to report clinical outcomes of patients with vaginal melanoma (VaM) or vulvar melanoma (VuM) who were treated with immune checkpoint inhibitors (ICI) and discuss the development of immune‐related adverse events (irAE). Materials and Methods. This is a retrospective case series of patients diagnosed with VaM or VuM between July 2011 and September 2022 at the University of Virginia, Emily Couric Clinical Cancer Center. Patient demographics, disease characteristics, treatment outcomes, and adverse events were abstracted. The primary outcome was incidence of irAE. Results. Eight patients were included in this study, four with VaM and four with VuM. Most (n = 6) had local or regional disease at first presentation, and 25% (n = 2) presented with distant metastasis. All patients received a CTLA‐4 inhibitor and 75% (n = 6) received PD‐1 inhibitor alone or in combination with a CTLA‐4 inhibitor. Most (75%, n = 6) patients experienced irAE. Of those who had irAE, 83% (n = 5) required therapy interruption or discontinuation. Most (66%, n = 4) underwent ICI rechallenge of which 75% (n = 3) experienced subsequent irAE. Of all patients in the series, 75% of patients (n = 6) had partial or complete response to ICI. Conclusion. This series is the first to detail incidence of irAEs and ICI rechallenges in vulvovaginal melanoma. Our findings indicate that while ICIs are effective, their use is associated with significant irAE development. Rechallenge of ICI after irAE is feasible but associated with risk of recurrent/new irAE. Further studies are needed to better quantify this risk. [ABSTRACT FROM AUTHOR]

Introduction. Triple‐negative breast cancer (TNBC) is a subgroup of breast cancer characterized by the absence of estrogen and the human epidermal 2 receptor and also a lack of targeted therapy options. Chemotherapy has so far been the only approved treatment option, and patients with metastatic cancer have a dismal prognosis with a median overall survival (OS) of approximately 14 months. Identification of druggable targets for metastatic TNBC is therefore of special interest. Methods. A systematic search was performed, to review the existing evidence on targeted therapies in metastatic TNBC. Results. A total of 37 phase 2/3 studies were identified, evaluating 29 different targeted agents. In this review, results on progression free survival (PFS) and OS are presented. Conclusion. In most of the studies included, no improvement was observed for neither PFS nor OS; however, a few studies did show improvement with targeted agents and have led to new treatment options in subgroups of patients. The antibody drug conjugate, sacituzumab govitecan, demonstrated superior PFS and OS in comparison to chemotherapy. Immunotherapy with checkpoint inhibitors such as atezolizumab and pembrolizumab is now recommended as a first‐line treatment option for patients with expression a PD‐L1 positive tumor. Finally, the poly adenosine diphosphate‐ribose polymerase (PARP) inhibitors talazoparib and olaparib are recommended, as first‐line treatment options in patients with metastatic breast cancer and a germline BRCA mutation, but an immune checkpoint inhibitor should be considered for the subset of these patients who are PD‐L1 positive. [ABSTRACT FROM AUTHOR]

Editorial. Introduces a series of articles focusing on the treatment of inflammatory bowel diseases. Increased competition in the research of immunopharmacology; Maintenance therapy by oral mesalazine and glucocorticosteroids; Immunotherapy; Ileostomy; Alternative treatments.

In this paper, an antitumour model for characterising radiotherapy and immunotherapy processes at different fixed times is proposed. The global attractiveness of the positive periodic solution for each corresponding subsystem is proved with the integral inequality technique. Then, based on the differentiability of the solutions with respect to the initial values, the eigenvalues of the Jacobian matrix at a fixed point corresponding to the tumour-free periodic solution are determined, resulting in a sufficient condition for local stability. The solutions to the ordinary differential equations are compared, the threshold condition for the global attractiveness of the tumour-free periodic solution is provided in terms of an indicator R 0 , and the permanence of a system with at least one tumour-present periodic solution is investigated. Furthermore, the effects of the death rate, effector cell injection dosage, therapeutic period, and effector cell activation rate on indicator R 0 are determined through numerical simulations, and the results indicate that radioimmunotherapy is more effective than either radiotherapy or immunotherapy alone. [ABSTRACT FROM AUTHOR]

Immunotherapy is one of the most recent approaches for controlling and curing malignant tumors. In this paper, we consider a mathematical model of periodically pulsed immunotherapy using CD4+ T cells and an antitumor cytokine. Mathematical analyses are performed to determine the threshold of a successful treatment. The interindividual variability is explored by one-, two-, and three-parameter bifurcation diagrams for a nontreatment case. Numerical simulation conducted in this paper shows that (i) the tumor can be regulated by administering CD4+ T cells alone in a patient with a strong immune system or who has been diagnosed at an early stage, (ii) immunotherapy with a large amount of an antitumor cytokine can boost the immune system to remit or even to suppress tumor cells completely, and (iii) through polytherapy the tumor can be kept at a smaller size with reduced dosages. [ABSTRACT FROM AUTHOR]

Background. Mutations in SLC25A32 in humans cause late-onset exercise intolerance, which is associated with various neurological and metabolic diseases. However, its specific mechanism of action in tumour development is poorly understood owing to the lack of multiomics integrated analysis of SLC25A32 in pan-cancer. Methods. We used various analytical tools to comprehensively investigate the transcription, protein level, and promoter methylation of SLC25A32. Furthermore, the GSCA and cBioPortal databases were used to evaluate the inheritance impact and epigenetic alterations of SLC25A32 in pan-cancer. SLC25A32 expression and the prognostic significance of copy number alterations in multiple cancers were compared using the UCSCXenaShiny and GEPIA2.0 platforms, and its specific function in breast cancer was experimentally verified. Results. SLC25A32 is abnormally expressed at the transcriptional and protein levels in most cancer types, with aberrant DNA promoter methylation and significant gene amplification in most tumours. SLC25A32 is significantly associated with the survival prognosis of some cancers, immune infiltrating cells, tumour stemness, and immune-related markers. SLC25A32 knockdown decreased breast tumour cell proliferation, invasion, and metastasis. Conclusions. This study aimed to reveal SLC25A32 as a novel prognostic biomarker for pan-cancer prediction and immunotherapy efficacy and specifically describes its underlying mechanism of action in breast cancer. SLC25A32 is widely differentially expressed in pan-cancer with prognostic significance and is correlated with immune infiltration. Additionally, it can affect breast cancer occurrence and development. [ABSTRACT FROM AUTHOR]

Immunotherapy is one of the future treatments applicable in most cases of cancer including malignant cancer. Malignant cancer usually prevents some genes, e.g., p53 and pRb, from controlling the activation of the cell division and the cell apoptosis. In this paper, we consider the interactions among the cancer cell population, the effector cell population that is a part of the immune system, and cytokines that can be used to stimulate the effector cells called the IL-2 compounds. These interactions depend on both time and spatial position of the cells in the tissue. Mathematically, the spatial movement of the cells is represented by the diffusion terms. We provide an analytical study for the constant equilibria of the reaction-diffusion system describing the above interactions, which show the initial behaviour of the tissue, and we conduct numerical simulation that shows the dynamics along the tissue that represent the immunotherapy effects. In this case, we also consider the steady-state conditions of the system that show the long-time behaviour of these interactions. [ABSTRACT FROM AUTHOR]

Background. Chimeric antigen receptor (CAR) T cell therapy, a "living drug" immunotherapy, harnesses the power of T-cells from a patient (autologous) or healthy donor (allogeneic) to target and kill cancer cells and has shown unprecedented outcomes in patients with relapsed and refractory malignancies. Treatment with CAR-T cells requires the application of unique skillsets in recognised specialist centres for successful outcomes and requires management by the multidisciplinary team incorporating the specialist pharmacist. Method. A multimodal research strategy was employed for this literature review whereby PubMed, Google Scholar, Embase, Stella Library Search, EMA website, and EBMT website were sources of information. The search was limited from 2020 onwards with key terms referring to CAR-T cell therapy. Results and Discussion. There are six CAR-T cell products currently approved by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) which target haematological malignancies with abundant clinical trials underway exploring new and improved CAR designs and antigen targets. As CAR-T cell therapy is an advanced therapy medicinal product (ATMP), there is need for an extensive regulatory framework underpinning its safety and efficacy. The clinical pharmacist plays an integral role in the provision of safe and effective CAR-T cell therapy including governance, operational and clinical aspects of treatment. Pharmacists may also be involved through provision of "Qualified Person" (QP) expertise in clinical trials and for release within hospitals under certain circumstances. There is a need for harmonised and accessible guidance on the clinical delivery of ATMPs such as CAR-T cells, with fully delineated responsibilities of pharmacists involving the oversight and supervision of CAR-T cell treatment. Conclusion. There is an unmet need to provide suitable and applicable literature for clinical pharmacists who are involved in the delivery of CAR-T cells. We have provided an overview of T-cell biology and an explanation of CAR-T cell design and the biomanufacturing process. We reviewed the complex and multifaceted treatment cycle requiring considerable logistics, and described the involvement of the clinical pharmacist in each part of this cycle from patient selection to postinfusion care. Finally, we look to the challenges and future opportunities that will require the involvement of the clinical pharmacist. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy, which reactivates weakened immune cells of cancer patients, has yielded great success in recent years. Among immunotherapeutic agents, immune checkpoint inhibitors have been of particular interest and have gained approval by the FDA for treatment of cancers. Immune checkpoint blockade through targeting programmed cell death protein-1 (PD-1) has demonstrated promising antitumor effects in cancer immunotherapy of many different solid and hematologic malignancies. However, despite promising results, a favorable response is observed only in a fraction of patients, and there is still lack of a single therapy modality with curative ability. In this paper, we review the current and future perspectives of PD-1/L1 blockade in cancer immunotherapy, with a particular focus on predictive biomarkers of response to therapy. We also discuss the adverse events associated with PD-1/L1/2 inhibitors, ranging from severe life-threatening conditions such as autoimmune myocarditis to mild and moderate reactions such as skin rashes, and explore the potential strategies for improving the efficacy of immunotherapy with PD-1/L1 checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success. [ABSTRACT FROM AUTHOR]

While it is generally accepted that Subcutaneous Injection Immunotherapy (SCIT) and Sublingual Immunotherapy (SLIT) are both efficacious, there is not yet a significant amount of information regarding their comparative efficacy. In this paper, we performed a retrospective chart review and compared treatment results in two groups of patients (both with nasal allergies with or without asthma) that were treated either with SCIT or SLIT. Both treatment modalities were found to be of similar efficacy. [ABSTRACT FROM AUTHOR]

Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems. [ABSTRACT FROM AUTHOR]

The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multidisciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles. [ABSTRACT FROM AUTHOR]

Treatment of patients with glioblastoma multiforme (GBM) remains to be a challenge with a median survival of 14.6 months following diagnosis. Standard treatment options include surgery, radiation therapy, and systemic chemotherapy with temozolomide. Despite the fact that the brain constitutes an immunoprivileged site, recent observations after immunotherapies with lysate from autologous tumor cells pulsed on dendritic cells (DCs), peptides, protein, messenger RNA, and cytokines suggest an immunological and even clinical response from immunotherapies. Given this plethora of immunomodulatory therapies, this paper gives a structure overview of the state-of-the art in the field. Particular emphasis was also put on immunogenic antigens as potential targets for a more specific stimulation of the immune system against GBM [ABSTRACT FROM AUTHOR]

The advancement of cancer immunotherapy faces barriers which limit its efficacy. These include weak immunogenicity of the tumor, as well as immunosuppressive mechanisms which prevent effective antitumor immune responses. Recent studies suggest that aberrant expression of cancer testis antigens (CTAs) can generate robust antitumor immune responses, which implicates CTAs as potential targets for immunotherapy. However, the heterogeneity of tumor cells in the presence and quantity of CTA expression results in tumor escape from CTA-specific immune responses. Thus, the ability tomodulate the tumor cell epigenome to homogenously induce expression of such antigens will likely render the tumor more immunogenic. Additionally, emerging studies suggest that suppression of antitumor immune responses may be overcome by reprogramming innate and adaptive immune cells. Therefore, this paper discusses recent studies which address barriers to successful cancer immunotherapy and proposes a strategy of modulation of tumor-immune cell crosstalk to improve responses in carcinoma patients. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumorinfiltrating lymphocytes (TILs) and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a life-threatening haematological malignancy for which standard therapy is inadequate. Autologous stem cell transplantation is a relatively effective treatment, but residual malignant sites may cause relapse. Allogeneic transplantation may result in durable responses due to antitumour immunity mediated by donor lymphocytes. However, morbidity and mortality related to graft-versus-host disease remain a challenge. Recent advances in understanding the interaction between the immune system of the patient and the malignant cells are influencing the design of clinically more efficient study protocols for MM. Cellular immunotherapy using specific antigen-presenting cells (APCs), to overcome aspects of immune incompetence in MMpatients, has received great attention, and numerous clinical trials have evaluated the potential for dendritic cell (DC) vaccines as a novel immunotherapeutic approach. This paper will summarize the data investigating aspects of immunity concerning MM, immunotherapy for patients with MM, and strategies, on the way, to target the plasma cell more selectively.We also include theMM antigens and their specific antibodies that are of potential use for MM humoral immunotherapy, because they have demonstrated the most promising preclinical results. [ABSTRACT FROM AUTHOR]

Patients with chronic hepatitis C virus (HCV) can develop systemic cryoglobulinemic vasculitis. Combination of pegylatedinterferon α and ribavirin is the first-line treatment of this condition. However, in case of severe or life-threatening manifestations, absence of a virological response, or autonomized vasculitis, immunotherapy (alone or in addition to the antiviral regimen) is necessary. Rituximab is to date the only biologic with a sufficient level of evidence to support its use in this indication. Several studies have demonstrated that rituximab is highly effective when cryoglobulinaemic vasculitis is refractory to antiviral regimen, that association of rituximab with antiviral regimen may induce a better and faster clinical remission, and, recently, that rituximab is more efficient than traditional immunosuppressive treatments. Some issues with regard to the optimal dose of rituximab or its use as maintenance treatment remain unsolved. Interestingly, in balance with this anti-inflammatory strategy, a recent pilot study reported the significant expansion of circulating regulatory T lymphocytes with concomitant clinical improvement in patients with refractory HCV-induced cryoglobulinaemic vasculitis using low dose of subcutaneous interleukin-2. This paper provides an updated overview on the place of immunotherapy, especially biologics, in the management of HCV-induced cryoglobulinaemic vasculitis. [ABSTRACT FROM AUTHOR]

Lung cancers remain one of the most common and deadly cancers in the world today (12.5% of newly diagnosed cancers) despite current advances in chemo- and radiation therapies. Often, by the time these tumors are diagnosed, they have already metastasized. These tumors demonstrate the classic hallmarks of cancer in that they have advanced defensive strategies allowing them to escape various standard oncological treatments. Immunotherapy is making inroads towards effectively treating other fatal cancers, such as melanoma, glioblastoma multiforme, and castrate-resistant prostate cancers. This paper will cover the escape mechanisms of bronchogenic lung cancer thatmust be overcome before they can be successfully treated.We also review the history of immunotherapy directed towards lung cancers. [ABSTRACT FROM AUTHOR]

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells,myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response. [ABSTRACT FROM AUTHOR]

Metastatic melanoma is still associated with a poor prognosis, and there is increasing interest in immunotherapy alone or in combination with other adjuvant therapies. Γδ T lymphocytes play a pivot role in the immune response against cancer, but while γδ-based immunotherapy is already a clinical reality for several solid tumors, data on melanoma are still limited and fragmented. This systematic review presents preclinical and clinical evidence for a role of γδ T lymphocytes in immunotherapeutic strategies for advanced melanoma and discusses research state of the art and future perspectives. Current strategies focus on in vivo stimulation, and ex vivo adoptive therapy and vaccination; results are promising, but further studies are needed to better investigate the interactions in tumoral microenvironment and to improve clinical efficacy of immunotherapeutic protocols. [ABSTRACT FROM AUTHOR]

In hematologic malignancies, the microenvironment is often characterized by nonneoplastic cells with peculiar phenotypic and functional features. This is particularly true in Hodgkin's lymphoma (HL), in which T lymphocytes surrounding Hodgkin's Reed- Sternberg cells are essentially polarized towards a memory T-helper type 2 phenotype. In this paper we will first evaluate the main processes modulating T-cell recruitment towards the lymph node microenvironment in HL, especially focusing on the role played by cytokines.We will then consider the most relevant mechanisms of immune escape exerted by neoplastic cells in order to evade antitumor immunity. The potential pathogenetic and prognostic impact of regulatory T cells in such a context will be also described.We will finally overview some of the strategies of cellular immunotherapy applied in patients with HL. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations. [ABSTRACT FROM AUTHOR]

The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI--IL-1 and ST2--IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI--IL-1 as well as ST2--IL-33 pathways may promise a disease-modifying approach in the future. [ABSTRACT FROM AUTHOR]

Portulaca oleracea L. (P. oleracea) or purslane is a plant from the Portulacaceae family, which is used as food and traditional medicine for various diseases. This review article provides comprehensive information on the antioxidant, immunomodulatory, and anti-inflammatory properties of P. oleracea and its constituents. The literature survey of the different databases until the end of June 2023 was explored based on the keywords including the "P. oleracea, purslane, anti-inflammatory, immunomodulatory, and antioxidant properties." The plant contains flavonoids, alkaloids, terpenoids, fatty acids, vitamins, minerals, and some other compounds. The results indicated that P. oleracea and its constituents showed anti-inflammatory and immunomodulatory properties through reduction of inflammatory mediators including interferon gama (IFN-γ), interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), and nitric oxide. Improvement in cytokines' serum levels (IFN-γ, IL-10, and IL-4) and increased IgG and IgM serum levels, as well as reduction of IgE, phospholipase A2, and total protein were demonstrated for P. oleracea. The plant and its constituents also improved oxidative stress by reduction of oxidant and increase of antioxidant markers. P. oleracea could be considered as an effective remedy for various inflammatory and immune diseases. [ABSTRACT FROM AUTHOR]

Background. PANoptosis has been a research hotspot, but the role of PANoptosis in hepatocellular carcinoma (HCC) remains widely unknown. Drug resistance and low response rate are the main limitations of chemotherapy and immunotherapy in HCC. Thus, construction of a prognostic signature to predict prognosis and recognize ideal patients for corresponding chemotherapy and immunotherapy is necessary. Method. The mRNA expression data of HCC patients was collected from TCGA database. Through LASSO and Cox regression, we developed a prognostic signature based on PANoptosis-related genes. KM analysis and ROC curve were implemented to evaluate the prognostic efficacy of this signature, and ICGC and GEO database were used as external validation cohorts. The immune cell infiltration, immune status, and IC50 of chemotherapeutic drugs were compared among different risk subgroups. The relationships between the signature and the efficacy of ICI therapy, sorafenib treatment, and transcatheter arterial chemoembolization (TACE) therapy were investigated. Result. A 3-gene prognostic signature was constructed which divided the patients into low- and high-risk subgroups. Low-risk patients had better prognosis, and the risk score was proved to be an independent predictor of overall survival (OS), which had a well predictive effect. Patients in high-risk population had more immunosuppressive cells (Tregs, M0 macrophages, and MDSCs), higher TIDE score and TP53 mutation rate, and elevated activity of base excision repair (BER) pathways. Patients with low risk benefited more from ICI, TACE, and sorafenib therapy. The predictive value of the risk score was comparable with TIDE and MSI for OS under ICI therapy. The risk score could be a biomarker to predict the response to ICI, TACE, and sorafenib therapy. Conclusion. The novel signature based on PANoptosis is a promising biomarker to distinguish the prognosis predict the benefit of ICI, TACE, and sorafenib therapy, and forecast the response to them. [ABSTRACT FROM AUTHOR]

Objective. To investigate the oncogenic effect and clinical significance of RAC2 in pancarcinoma from the perspective of tumor immunity and cancer stem cell. Methods. After in-depth mining of TCGA, GEO, UCSC, and other databases, basic information of the RAC2 gene and its expression in tumor tissues as well as the relationship between RAC2 and tumor were analyzed based on survival, mutation, immune microenvironment, tumor stemness, and enrichment analysis on related pathways. Results. RAC2 mRNA expression was increased in most tumor tissues and was associated with their prognosis. Compared to normal tissues, the RAC2 mutation rate was higher in patients with skin melanoma, uterine sarcoma, and endometrial cancer. RAC2 had a strong relation with immune cell infiltration, immunomodulators, immunotherapy markers, cancer stem cell of THYM, and immune-related pathways. Conclusions. This study explored the potential importance of RAC2 in the prognosis, immunotherapy, and cancer stem cell of 33 cancers, laying the foundation for mechanistic experiments and its future application in clinical practice. However, the results using bioinformatics methods could be affected by the differences in patients across databases. Thus, the present results were preliminary and required further experimental validation. [ABSTRACT FROM AUTHOR]

Objectives. The most common subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC), has a high heterogeneity and aggressive nature. The basement membrane (BM) is known to play a vital role in tumor metastasis. BM-related genes remain untested in ccRCC, however, in terms of their prognostic significance. Methods. BM-related genes were gleaned from the most recent cutting-edge research. The RNA-seq and clinical data of the ccRCC were obtained from TCGA and GEO databases, respectively. The multigene signature was constructed using the univariate Cox regression and the LASSO regression algorithm. Then, clinical features and prognostic signatures were combined to form a nomogram to predict individual survival probabilities. Using functional enrichment analysis and immune-correlation analysis, we investigated potential enrichment pathways and immunological characteristics associated with BM-related-gene signature. Results. In this study, we built a model of 20 BM-related genes and classified them as high-risk or low-risk, with each having its anticipated risk profile. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group in the TCGA cohort, as was confirmed by the testing dataset. Functional analysis showed that the BM-based model was linked to cell-substrate adhesion and tumor-related signaling pathways. Comparative analysis of immune cell infiltration degrees and immune checkpoints reveals a central role for BM-related genes in controlling the interplay between the immune interaction and the tumor microenvironment of ccRCC. Conclusions. We combined clinical characteristics known to predict the prognosis of ccRCC patients to create a gene signature associated with BM. Our findings may also be useful for forecasting how well immunotherapies would work against ccRCC. Targeting BM may be a therapeutic alternative for ccRCC, but the underlying mechanism still needs further exploration. [ABSTRACT FROM AUTHOR]

Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining Re188-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain Re188-radioimmunoconjugates in high radiochemical purity starting from the generator eluted Re188ReO4-. The aim of this paper is to provide a short overview on Re188-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. [ABSTRACT FROM AUTHOR]

Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included. [ABSTRACT FROM AUTHOR]

GINS2 is overexpressed in several cancers, but little is known about its role in osteosarcoma (OS). A series of in vivo and in vitro experiments were conducted to explore the role of GINS2 in OS. In this study, we demonstrated that GINS2 was found to be highly expressed in OS tissues and cell lines, which was associated with poor outcomes in OS patients. GINS2 knockdown hindered the growth and induced apoptosis in OS cell lines in vitro. Furthermore, GINS2 knockdown effectively inhibited the growth of a xenograft tumor in vivo. By using an Affymetrix gene chip and intelligent pathway analysis, it was demonstrated that the GINS2 knockdown could reduce the expression of several targeted genes and reduce the activity of the MYC signaling pathway. Mechanically, LC-MS, CoIP, and rescue experiments revealed that GINS2 promoted tumor progression through the STAT3/MYC axis in the OS. Moreover, GINS2 was associated with tumor immunity and may be a potential immunotherapeutic target for OS. [ABSTRACT FROM AUTHOR]

Background. The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods. The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results. In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion. Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future. [ABSTRACT FROM AUTHOR]

Background. The tumor microenvironment (TME) has gradually entered the vision of researchers and is becoming a vital part of the occurrence of cervical squamous cell carcinoma (CSCC). However, understanding the specific composition of TME still confront enormous challenges, particularly immune and stromal components. Methods. In this study, we performed an unsupervised cluster analysis to determine the immunogenic cell death-associated subtype of CSCC patients. The differences in immune status, genomic alteration, and clinical outcomes between each subtype were compared. Subsequently, we screened vital prognostic factors. The HPA database was employed to verify the protein localization and the expression level between cancer and adjacent tissues. Results. CSCC patients were divided into three subtypes according to the expression of immunogenic cell death-associated genes. Cluster C has the highest survival rate because of the lower activation of tumor-related pathways. The immune score and stromal score of patients with Cluster B were the highest, so it may be considered that stromal tissue inhibits the anti-tumor effect of immunocytes. In addition, we constructed a risk score based on immunogenic cell death-associated genes to screen for vital markers. We systematically revealed the genomic alteration of vital markers. Conclusions. We have established a novel immunogenic cell death-associated risk scoring system in CSCC, and the expression of immunogenic cell death-associated genes may be a valuable biomarker for immunotherapy strategies. Our work may contribute to the development of new immunomodulators and develop new precision immunotherapies for CSCC. [ABSTRACT FROM AUTHOR]

DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues (p < 0.01). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, p = 0.048). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA (p < 0.05). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues (p = 0.011). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues (p = 0.011). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy. [ABSTRACT FROM AUTHOR]