Innate Immunity Suppression in Glioma, Reason, Mechanisms and Potential Treatments

Glioblastoma (GBM) is the most lethal primary central nervous system malignancy, with intrinsic immunosuppressive traits severely limiting the efficacy of conventional and immunotherapeutic regimens. This paper systematically elaborates the core causes, multi-layered molecular and cellular mechanisms, and targeted therapeutic strategies of innate immune suppression in GBM. It demonstrates that tumour-intrinsic oncogenic mutations, central nervous system immune privilege, and tumour microenvironment (TME) remodeling synergistically construct an immunosuppressive background to block innate anti-tumour surveillance. Mechanistically, GBM impairs innate immune activation via diminished DAMP release, defective pattern-recognition receptor (PRR) signaling transduction, and functional reprogramming of microglia, macrophages, NK cells and dendritic cells. This paper shows that innate immune suppression can not be reversed by single-target therapy using examples such as emerging PRR-targeted agonists and myeloid-modulatory interventions. It highlights the restoration of innate immune sensing and TME immune as the core direction for future GBM immunotherapy, providing systematic theoretical support for clinical translational research.