Fig. 3

Roles of HLA-G in tumor immune microenvironment. HLA-G can inhibit the cytotoxicity and chemotaxis of T cells and foster the differentiation of the CD4 + T cells into Treg cells through direct binding, while sHLA-G can drive Th2 cells polarization and potentiate TIM-3 expression to indirectly exert suppressive effects on T cells. Similarly, HLA-G dampens NK cells cytotoxicity, chemotaxis, and migration, while inducing apoptosis and senescence. Moreover, the interaction between HLA-G and ILTs restrains the proliferation of neutrophils, impairs the proliferation, differentiation, chemotaxis, and antibody secretion of B cells, and triggers a shift in macrophage polarization toward M2. MDSC proliferation and accumulation are facilitated by HLA-G. Additionally, HLA-G impairs the activation and antigen-presenting function of DCs and promotes tolerogenic DCs induction. To note, tumor cells can transfer HLA-G to other tumor cells and effector immune cells, leading to the swift dissemination of immunosuppression. NK cells natural killer NK cells, MDSC myeloid-derived suppressor cell, DCs dendritic cells