Figure 2.

Mechanisms of PD-1/PD-L1 inhibitors resistance: PD-1/PD-L1 inhibitor resistance is divided into primary resistance and acquired resistance. Mechanisms of primary resistance include lack of tumor immunogenicity; T-cell rejection; lack of interferon responsiveness, such as IFNγ (interferon Gamma) and IFNα (interferon alpha); EGFR (epidermal growth factor receptor) mutations and ALK (anaplastic lymphoma kinase) rearrangements; local immunosuppressive factors within the tumor microenvironment, such as MDSC (myeloid-derived suppressor cell) and TIM (tumor-infiltrating myeloid cell). While, the mechanisms of acquired resistance may be related to the following factors: exhaustion and loss of T cell function; impaired processing or presentation of neoantigens; complexity of the tumor microenvironment; mutations in associated genes, such as STK11/LKB1; dysbiosis of the gut microbiome; lack of Memory T Cells and upregulation of other Immune Checkpoints, such as CTLA-4(cytotoxic T-lymphocyte antigen-4), TIM-3(T cell immunoglobulin and mucin domain-containing molecule-3), LAG-3(lymphocyte activation gene-3) and VISTA(V-domain Ig suppressor of T cell activation).