Immunology and prospects of immunotherapy against malignant gliomas: humoral immunity

Abstract

High-grade gliomas are aggressive brain tumors with limited survival rates. To date the maximum of survival benefit of conventional therapeutic options has been already reached and innovative treatment strategies, based on tumor biology are urgently needed. Generally, malignant gliomas, including glioblastoma, are immunologically “cold: neoplasms, with weak anti-tumor immune response and peritumoral inflammation, caused by reduced expression of neoantigens by tumor cells and restricted immunoreactivity of the microenvironment. The reduced immunogenicity of brain structures is conditioned by the absence of homing molecules for white blood cells on them, as well as the suppression of activated (CD178+) T cells by brain gangliosides. The cell population infiltrating malignant glioma is impoverished with cytotoxic T cells (CD8+ FOXP3–) and oppositely enriched with regulatory T cells and type 2 macrophages (M2). An effective anti-glioma immune response is resulted in increasing the total number of tumor-infiltrating lymphocytes and the CD8+ cell content; switching the functional activity of macrophages from M2 to M1 type. Integration of immunotherapeutic technologies (vaccines and monoclonal antibodies) into treatment strategies of malignant gliomas is relevant and promising approach based on biological features of the tumor.

Keywords

• high-grade gliomas
• immunotherapy
• humoral immunity
• monoclonal antibodies