Glioma tumor microenvironment and immunotherapy: past, present, and future

Gliomas constitute a major category of primary brain malignancies, characterized by limited therapeutic options and generally poor prognoses. Despite the promising outcomes of immunotherapies, particularly immune checkpoint inhibitors (ICIs), in various cancers, their clinical efficacy in gliomas has remained modest. This limited efficacy is largely attributed to the brain's immune-privileged status and the profoundly immunosuppressive nature of the glioma tumor microenvironment (TME). These challenges underscore the urgent need to improve understanding of the glioma TME and to develop innovative strategies that enhance the effectiveness of immunotherapies. This review provides a comprehensive overview of recent advances in glioma immunobiology and immunotherapy, with emphasis on ongoing clinical trials and emerging combinatorial strategies. Current efforts to combine ICIs with modalities such as radiotherapy and chemotherapy are highlighted, aiming to remodel the TME, improve antigen presentation, and stimulate more robust antitumor immune responses. The evolving landscape of glioma immunotherapy offers renewed hope for enhanced patient outcomes.Clinical trial registration Not applicable.