Search

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available as immune checkpoint inhibitors (ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response. Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1 (anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and signal-regulatory protein α (SIRPα). Functional mAbs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in mAbs targeting these immune checkpoint molecules and their potential applications.

Abstract Background Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count.

Background: Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives: The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method: We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results: Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions: When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-oncology has revolutionized the natural history of many cancers in the past decade, becoming a new therapeutic weapon. The identification of immune "checkpoints" (PD-1/CTLA-4) whose blockade stimulates anti-tumor immunity has changed outcomes for many ptients. However, immune checkpoint inhibitors (ICIs) produce novel response patterns across cancer types and can cause inflammatory side-effects known as immune-related adverse events (irAEs). Renal damage from ICIs is an infrequent event, and early diagnosis plays a key role in its treatment, so it is crucial to recognize and treat it early to avoid toxicities of all grades, as well as hospitalizations. Immunity plays a crucial role in fighting cancer, but tumours can evade the immune system and proliferate and metastasize. Enhancing immune responses is a new challenge in anticancer therapies. In this context, efficacy data are accumulating on immune checkpoint inhibitors and adjuvant therapies for various types of advanced-stage solid tumours. Unfortunately, immune-related adverse events are common. Although infrequent, renal toxicity may occur via several mechanisms and may require temporary or permanent drug suspension, renal biopsy, and/or immunosuppressive treatment. This short review aims to provide a practical approach to the multidisciplinary management of cancer patients with renal toxicity during treatment with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

A vital function of the immune system is the modulation of an evolving immune response. It is responsible for guarding against a wide variety of pathogens as well as the establishment of memory responses to some future hostile encounters. Simultaneously, it maintains self-tolerance and minimizes collateral tissue damage at sites of inflammation. In recent years, the regulation of T-cell responses to foreign or self-protein antigens and maintenance of balance between T-cell subsets have been linked to a distinct class of cell surface and extracellular components, the immune checkpoint molecules. The fact that both cancer and viral infections exploit similar, if not the same, immune checkpoint molecules to escape the host immune response highlights the need to study the impact of immune checkpoint blockade on viral infections. More importantly, the process through which immune checkpoint blockade completely changed the way we approach cancer could be the key to decipher the potential role of immunotherapy in the therapeutic algorithm of viral infections. This review focuses on the effect of programmed cell death protein 1/programmed death-ligand 1 blockade on the outcome of viral infections in cancer patients as well as the potential benefit from the incorporation of immune checkpoint inhibitors (ICIs) in treatment of viral infections. [ABSTRACT FROM AUTHOR]

Background: This study aims to describe COVID-19–related clinical outcomes after immunotherapies (ICIs) for cancer patients. Methods: In this meta-analysis, we searched databases to collect data that addressed outcomes after immunotherapies (ICIs) during the COVID-19 pandemic. The primary endpoint was COVID-19–related mortality. Secondary endpoints included COVID-related hospital readmission, emergency room (ER) visits, opportunistic infections, respiratory complications, need for ventilation, and thrombo-embolic events. Pooled event rates (PERs) were calculated and a meta-regression analysis was performed. Results: A total of 262 studies were identified. Twenty-two studies with a total of forty-four patients were eligible. The PER of COVID-19–related mortality was 39.73%, while PERs of COVID-19–related ER visits, COVID-19–related pulmonary complications, and COVID-19–related ventilator needs were 40.75%, 40.41%, and 34.92%, respectively. The PER of opportunistic infections was 34.92%. The PERs of the use of antivirals, antibiotics, steroids, prophylactic anticoagulants, and convalescent plasma were 62.12%, 57.12%, 51.36%, 41.90%, and 26.48%, respectively. There was a trend toward an association between previous respiratory diseases and COVID-19–related mortality. Conclusion: The rates of COVID-19–related mortality, ER visits, pulmonary complications, need for a ventilator, and opportunistic infections are still high after ICIs during the COVID-19 pandemic. There was a trend toward an association between previous respiratory diseases and COVID-19–related mortality. [ABSTRACT FROM AUTHOR]

A vital function of the immune system is the modulation of an evolving immune response. It is responsible for guarding against a wide variety of pathogens as well as the establishment of memory responses to some future hostile encounters. Simultaneously, it maintains self-tolerance and minimizes collateral tissue damage at sites of inflammation. In recent years, the regulation of T-cell responses to foreign or self-protein antigens and maintenance of balance between T-cell subsets have been linked to a distinct class of cell surface and extracellular components, the immune checkpoint molecules. The fact that both cancer and viral infections exploit similar, if not the same, immune checkpoint molecules to escape the host immune response highlights the need to study the impact of immune checkpoint blockade on viral infections. More importantly, the process through which immune checkpoint blockade completely changed the way we approach cancer could be the key to decipher the potential role of immunotherapy in the therapeutic algorithm of viral infections. This review focuses on the effect of programmed cell death protein 1/programmed death-ligand 1 blockade on the outcome of viral infections in cancer patients as well as the potential benefit from the incorporation of immune checkpoint inhibitors (ICIs) in treatment of viral infections.

The cancer cells that are not normal can grow into tumors, invade surrounding tissues, and travel to other parts of the body via the lymphatic or circulatory systems. Interleukins, a vital class of signaling proteins, facilitate cell-to-cell contact within the immune system. A type of non-coding RNA known as lncRNAs mediates its actions by regulating miRNA-mRNA roles (Interleukins). Because of their dual function in controlling the growth of tumors and altering the immune system's response to cancer cells, interleukins have been extensively studied concerning cancer. Understanding the complex relationships between interleukins, the immune system, the tumor microenvironment, and the components of interleukin signaling pathways that impact the miRNA-mRNA axis, including lncRNAs, has advanced significantly in cancer research. Due to the significant and all-encompassing influence of interleukins on the immune system and the development and advancement of cancers, lncRNAs play a crucial role in cancer research by modulating interleukins. Their diverse effects on immune system regulation, tumor growth encouragement, and tumor inhibition make them appealing candidates for potential cancer treatments and diagnostics. A deeper understanding of the relationship between the biology of interleukin and lncRNAs will likely result in more effective immunotherapy strategies and individualized cancer treatments. [ABSTRACT FROM AUTHOR]

Background: This study aims to describe COVID-19–related clinical outcomes after immunotherapies (ICIs) for cancer patients. Methods: In this meta-analysis, we searched databases to collect data that addressed outcomes after immunotherapies (ICIs) during the COVID-19 pandemic. The primary endpoint was COVID-19–related mortality. Secondary endpoints included COVID-related hospital readmission, emergency room (ER) visits, opportunistic infections, respiratory complications, need for ventilation, and thrombo-embolic events. Pooled event rates (PERs) were calculated and a meta-regression analysis was performed. Results: A total of 262 studies were identified. Twenty-two studies with a total of forty-four patients were eligible. The PER of COVID-19–related mortality was 39.73%, while PERs of COVID-19–related ER visits, COVID-19–related pulmonary complications, and COVID-19–related ventilator needs were 40.75%, 40.41%, and 34.92%, respectively. The PER of opportunistic infections was 34.92%. The PERs of the use of antivirals, antibiotics, steroids, prophylactic anticoagulants, and convalescent plasma were 62.12%, 57.12%, 51.36%, 41.90%, and 26.48%, respectively. There was a trend toward an association between previous respiratory diseases and COVID-19–related mortality. Conclusion: The rates of COVID-19–related mortality, ER visits, pulmonary complications, need for a ventilator, and opportunistic infections are still high after ICIs during the COVID-19 pandemic. There was a trend toward an association between previous respiratory diseases and COVID-19–related mortality.

Opinion Statement: Immune checkpoint inhibitors (ICIs) represent a breakthrough in the management of many hard-to-treat cancers over the past decade with demonstrable improvement in survival outcomes. We reviewed the state of the art of ICIs in neuroendocrine neoplasms (NENs). While ICIs have become part of the standard of care for the management of small cell lung cancer (SCLC), their role is still unclear in the management of extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) as well as in the management of well-differentiated neuroendocrine tumors (NETs). Conflicting results derived from the various studies in NETs and EP NECs therefore for specific settings, such as the lung NETs, or therapeutic regimen, e.g., combo vs single agent, for ICIs benefit. Therefore, at the moment, no ICIs approach is justified for NETs and EP NECs in clinical practice. Future investigations should be designed with the aim to overcome the several limitations of the current trials, e.g., lacking of a central pathology review or heterogeneity of the cohorts, in order to reduce the risk of biases. Future trials combining ICIs with other biological agents are welcome. This review aims to provide a comprehensive overview of the biological rationale and evolving clinical applications of the use of ICIs in the management of NENs (both well-differentiated and poorly differentiated groups). [ABSTRACT FROM AUTHOR]

Cancer displays high levels of heterogeneity and mutation potential, and curing cancer remains a challenge that clinicians and researchers are eager to overcome. In recent years, the emergence of cancer immunotherapy has brought hope to many patients with cancer. Cancer immunotherapy reactivates the immune function of immune cells by blocking immune checkpoints, thereby restoring the anti-tumor activity of immune cells. However, immune-related adverse events are a common complication of checkpoint blockade, which might be caused by the physiological role of checkpoint pathways in regulating adaptive immunity and preventing autoimmunity. In this context, the intestinal microbiota has shown great potential in the immunotherapy of cancer. The intestinal microbiota not only regulates the immune function of the body, but also optimizes the therapeutic effect of immune checkpoint inhibitors, thus reducing the occurrence of complications. Therefore, manipulating the intestinal microbiota is expected to enhance the effectiveness of immune checkpoint inhibitors and reduce adverse reactions, which will lead to new breakthroughs in immunotherapy and cancer management. Video abstract [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at investigating the value of applying positron emission tomography (PET) to early predict the effect of immune checkpoint inhibitors (ICIs) in malignant tumors. Methods: Electronic databases MEDLINE/PubMed, EMBASE, and Cochrane Library were searched to identify relevant trials. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The results were analyzed utilizing SPSS 19.0 statistical software. Subgroup analyses were implemented based on primary tumors, study designs, continents, type of ICIs, evaluation index of PET, and evaluated PET timing. Results: Fifteen studies incorporating 664 individuals were eligible. Compared with PET nonresponse group, PET response group displayed a significantly prolonged PFS (HR 0.27, 95% CI [0.16, 0.44]; P < 0.001) and OS (HR 0.56, 95% CI [0.48, 0.65]; P < 0.001). Analogical outcomes were obtained in subgroup analyses of PFS in non-small cell lung cancer, prospective, America, ipilimumab, nivolumab/pembrolizumab combined ipilimumab, PET Response Criteria in Solid Tumors (PERCIST), baseline PET and early PET timing arms without heterogeneity; so did OS in melanoma, retrospective, Europe, America, ipilimumab, nivolumab/pembrolizumab, PERCIST, baseline metabolic tissue volume, baseline standard uptake value, and baseline total lesion glycolysis, baseline PET timing, early PET timing and late PET timing arms. Conclusion: Our study demonstrated that PET was a promising approach to early predict the prognosis of ICIs for malignancies. [ABSTRACT FROM AUTHOR]

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient’s autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking.

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient's autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common types of cancer; notably, gastric cancer is one of the top five malignancies with regards to incidence and mortality rates. The symptoms of early gastric cancer are not typical, exhibiting only slight upper abdominal discomfort. When the symptoms become more obvious, the lesion has usually progressed to an advanced stage. Notably, >90% of inpatients already have locally advanced or metastatic gastric cancer at the time of initial diagnosis, with limited treatment options for advanced gastric cancer. These options include chemotherapy, targeted therapy and immune checkpoint inhibitors (ICIs). With regards to ICIs, the clinical benefit of monotherapy for advanced gastric cancer is limited; however, combinations of ICIs and other therapies may have clinical benefit. Relevant clinical studies have demonstrated that combinations of ICIs with chemotherapy, anti-vascular targeted therapy or other molecular targeted therapies, and the use of two ICIs, improve outcomes for patients with advanced gastric cancer. This article is a review of progress in the use of ICIs in combination with other therapies for the treatment of gastric cancer. The purpose of this article was to advance gastric cancer immunotherapy and to improve the overall therapeutic benefit for patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]