Fig. 1

The mechanisms by which cancer cells escape from immune attack of immune effector cells. Firstly, tumor-derived cytokines especially TGF-β remarkably reshape the tumor immune microenvironment. This immunosuppressive cytokine repertoire inhibits the functions of multiple effector cells, induces the differentiation of regulatory cells, and impedes the infiltration of T cells. Secondly, overexpressed immune checkpoints or their ligands such as PD-L1 on cancer cells promote the formation of exhausted TILs. Thirdly, cancer cells tend to harbor alterations in antigen processing machinery, which result in the loss of tumor-associated antigens and neoantigens. Mutations in major histocompatibility complex class I (MHC-I), proteasome subunits latent membrane protein, as well as transporter associated with antigen processing reduce the presentation of recognizable targets on cancer cells. Fourthly, overexpressed HLA-G on cancer cells binds to the inhibitory receptors on effector cells such as CTLs and NKs, leading to the suppression of the cytotoxic activities of these effector cells. Lastly, cancer cells could escape immune attack by downregulating NKG2D ligands including MICA, MICB, and UL16-binding protein. TAP transporter associated with antigen processing, MHC-I major histocompatibility complex class I, MICA/B MHC-I chain-related molecules A/B, IDO indoleamine 2, 3-dioxygenase, ULBP UL16-binding protein