Immune Microenvironment of Gliomas

Dear Colleagues,

Malignant gliomas are rapidly progressing, incurable tumors of the central nervous system (CNS). Numerous studies of human and experimental rodent gliomas have revealed considerable heterogeneity in the tumor microenvironment, which is composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells mostly consist of glioma-associated microglia and macrophages (GAMs), myeloid-derived suppressor cells (MDSCs), granulocytes, and T lymphocytes. Myeloid cells have a few intact innate immune functions, but instead of initiating antitumor immune responses, they are reprogrammed and secrete proinvasive and immunosuppressive molecules, supporting tumor growth and enabling effective antitumor T cell responses. Findings from linage tracing and single cell RNA sequencing studies have revealed cell type heterogeneity among immune infiltrates, a significant contribution of peripheral myeloid cells to GAMs, and specific functional responses of discrete subpopulations. Accumulating MDSCs inhibit cytotoxic responses mediated by natural killer cells and block the activation of tumor-reactive CD4⁺ T helper cells and cytotoxic CD8⁺ T cells. Malignant gliomas induce various states of T-cell dysfunction, resulting in decreased proliferative capacity and effector function. The presence of regulatory T cells contributes to the lack of effective immune activation against malignant gliomas. The complexity of cell-to-cell interactions in the glioma microenvironment is far from well understood. Identification of those mediators may facilitate the development of immunotherapies for gliomas, as immunomodulatory and immune evasion mechanisms employed by malignant gliomas are listed as the main obstacles to glioma immunotherapy. Tumor antigenic heterogeneity, an immunosuppressive microenvironment, unique properties of the CNS that limit T cell entry, and potential immune‐based toxicities impede the development of effective immunotherapies for gliomas. The low antigenicity of gliomas and the low abundance and perivascular location of CD8 T cells may further contribute to the limited clinical efficacy of checkpoint inhibitors in glioma patients. In this Special Issue, we will summarize and present new findings related to the heterogeneity and complexity of interactions between tumor and immune components in the glioma microenvironment.

Prof. Bozena Kaminska
Prof. Cristina Limatola
Guest Editors

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