Contributions of immune cell populations in the maintenance, progression, and therapeutic modalities of glioma

Abstract

Immunotherapies are becoming a promising strategy for malignant disease. Selectively directing host immune responses to target cancerous tissue is a milestone of human health care. The roles of the innate and adaptive immune systems in both cancer progression and elimination are now being realized. Defining the immune cell environment and identifying the contributions of each sub-population of these cells has lead to an understanding of the immunotherapeutic processes, and demonstrated the potential of the immune system to drive cancer shrinkage and sustained immunity against disease. Poorly treated diseases, such as high-grade glioma, suffer from lack of therapeutic efficacy and rapid progression. Immunotherapeutic success in other solid malignancies, such as melanoma, now provides the principals for which this treatment paradigm can be adapted for primary brain cancers. The central nervous system is complex, and relative contributions of immune sub-populations to high grade glioma progression are not fully characterized. Here, we summarize recent research in both animal and humans which add to the knowledge base of how innate and adaptive immune cells contribute to glioma progression, and outline work which has demonstrated their potential to elicit anti-tumorigenic responses. Additionally, we highlight Neuropilin 1, a cell surface receptor protein, describe its signaling functions in the context of immunity, and point to its potential to slow glioma progression.

Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment

“…The contribution of macrophages/microglia to the immunosuppressive TME of GBM and their prevalence within the tumor bulk suggest them to be attractive therapeutic targets for the immunotherapeutic targeting of GBM. As mentioned previously, microglia and macrophages in the TME adopt an immunosuppressive M2 phenotype ( 103 , 104 ). As also previously mentioned, microglia/macrophages express the CSF-1R and GBM cells secrete CSF-1 resulting in the switching of GBM macrophages/microglia to the immune inhibitory M2 phenotype.…”

“…Although immune cell infiltration is often viewed as a positive prognostic marker, it can also contribute to the pathology of GBM. Lymphocytes entering the tumor have been shown to downregulate costimulatory molecules such as CD28 and CD62L ( 103 ). The presence of immunosuppressive regulatory T cells within GBM tumors has been correlated with shorter recurrence-free survival.…”

“…The presence of immunosuppressive regulatory T cells within GBM tumors has been correlated with shorter recurrence-free survival. GBM associated microglia/macrophages, which constitute up to 30% of the GBM tumor bulk are of the immunosuppressive M2 phenotype ( 103 , 104 ). The expression of PD-L1 by these immunosuppressive M2 cells further contributes to local immunosuppression, as does their secretion of CCL22 which recruits regulatory T cells and MDSCs into the TME ( 103 , 104 ).…”