TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells

Abstract

This study is sought to determine the physiological mechanisms by which exosomes-encapsulated TIM-3 derived from melanoma cells might mediate CD4+ T cell immune function and macrophage M2 polarization in melanoma. Initially, exosomes were isolated from the human skin-derived melanoma cell line MV3for analysis of TIM-3 expression pattern. Next, the exosomes sourced from MV3 cells manipulated with sh-TIM-3 were co-incubated with CD4+ T cells to detect CD4+ T cell proliferation and MV3 cell migration and invasion, to observe the macrophage M2 polarization, and to determine levels of several EMT-related factors. Finally, melanoma nude mouse models were established to study the in vivo modulatory effects of TIM-3 from MV3 cells-derived exosomes. MV3 cells-derived exosomes inhibited CD4+ T cell immune function and promoted macrophage M2 polarization in melanoma. Our results revealed the abundance of TIM-3 in MV3 cells-derived exosomes. Of importance, silencing of TIM-3 shuttled by MV3 cells-derived exosomes improved CD4+ T cell immune function and inhibited macrophage M2 polarization to attenuate the growth and metastasis of melanoma cells. Collectively, MV3 cells-derived exosomes-loaded TIM-3 suppressed CD4+ T cell immune function and induced macrophage M2 polarization to improve occurrence and development of melanoma, therefore providing us with a potential therapeutic target for effectively combating melanoma.