Downregulation of exosomal MHC-I promotes glioma cells escaping from systemic immunosurveillance
Nanomedicine: Nanotechnology, Biology and Medicine(2022)
摘要
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 demonstrated 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.
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关键词
MHC-I,Exosomes,Systemic immunosurveillance,Antigen presentation,T cell activation
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