Tumor-cell-extrinsic mechanisms of immunotherapy resistance involve components other than tumor cells within the tumor microenvironment, including increased distribution of Th2 cells, M2 macrophages, and decreased tumor-infiltrating CD8+ T cells, DCs, Th1 cells, CD4+ T cells, and M1 macrophages (Aldea et al., 2021). This evidence concerns the gene CD8A and neoplasm.