The primary resistance mechanism to ICIs mainly includes: 1) a diminished expression of PD-L1 on tumor cells; 2) diminished response to ICIs due to tumor-intrinsic factors, such as genetic alterations within tumor cells that impact antigen presentation, interferon signaling, or downstream signaling pathways; 3) the loss of the IFN-γ signaling pathway; and 4) other factors that influence the enteric microbiome, effector T-cell infiltration in the tumor microenvironment (TME) and T-cell exhaustion. This evidence concerns the gene IFNG and neoplasm.