Current state and future of co-inhibitory immune checkpoints for the treatment of glioblastoma

In the interaction between a tumor and the immune system,immune checkpoints play an important role,and in tumor immune escape,co-inhibitory immune checkpoints are important.Immune checkpoint inhibitors(ICIs)can enhance the immune system's killing effect on tumors.To date,impressive progress has been made in a variety of tumor treatments;PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors.However,glioblastoma(GBM)still lacks an effective treatment.Recently,a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab.Therefore,the use of immune checkpoints in the treatment of GBM still faces many challenges.First,to clarify the mechanism of action,how different immune checkpoints play roles in tumor escape needs to be determined;which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined.Second,to optimize combination therapies,how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed.All of these concerns require extensive basic research and clinical trials.In this study,we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments,summarized the state of ICIs in preclinical studies and clinical trials involving GBM,and speculated on the therapeutic prospects of ICIs in the treatment of GBM.

New perspective on the treatment of rheumatic arthritis based on“strengthening body resistance(FúZhèng)”in the theory of co-inhibitory receptor-regulated T-cell immunity

Co-inhibitory receptors serve as crucial regulators of T-cell function,playing a pivotal role in modulating the delicate balance between immune tolerance and autoimmunity.Initially identified in autoimmune disease models,co-inhibitory receptors,including CTLA-4,PD-1,TIM-3,and TIGIT,were found to be integral to immune regulation.Their blockade or absence in these models resulted in the induction or exacerbation of autoimmune diseases.Additionally,scholars have observed that co-inhibitory receptors on lymphocytes hold the potential to influence the prognosis in the context of chronic inflammation.Consequently,the blocking of co-suppressor receptors has emerged as a novel therapeutic approach for inhibiting refractory inflammatory diseases,particularly rheumatoid arthritis.From the standpoint of traditional Chinese medicine(TCM),the treatment of rheumatoid arthritis based on the“strengthening body resistance(FúZhèng)”theory can be construed as the regulation of co-suppressor receptors to modulate the body’s immune function in combating chronic inflammation.This article provides a succinct overview of the role of co-suppressor receptors in anti-inflammatory processes and explores the research prospects of co-suppressor receptor intervention in the treatment of rheumatoid arthritis.The exploration integrates the“strengthening body resistance(FúZhèng)”theory with relevant Chinese medicine formulations.

T-cell Co-inhibitory Molecules in Sepsis-induced Immunosuppression： From Bench to Bedside

Sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in the Intensive Care Unit （ICU） Epidemiological studies have shown that the incidence of sepsis has been gradually increasing during the past decades,

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.