Downregulation of exosomal MHC-I promotes glioma cells escaping from systemic immunosurveillance

Tumor-derived exosomes are capable of inducing immune dysfunction and favoring the formation and progression of tumor. The major histocompatibility complex class I (MHC-I) plays a key role in antitumor immune responses by presenting tumor antigens to cytotoxic T lymphocytes. However, the role of tumor-derived circulating exosomal MHC-I on immune system activation remains unclear. We demon-strated that low level of glioma cells-derived exosomal MHC-I was associated with the dysfunction of CD8(+) T cells in immune activation and cytotoxicity. MHC-I upregulation in exosomes restored antigen presentation of glioma cells and activated CD8(+) T cells to exert robust antitumor immune response in combination with immune checkpoint blockade. Collectively, these data provided evidences for an important interplay between exosomal MHC-I and CD8(+) T cells to activate systemic antitumor immune response, and interpreted how glioma cells evaded immunosurveillance, induced immunosuppression and were resistant to immunotherapy from the perspective of systemic immunity. (C) 2022 Published by Elsevier Inc.