Tumor cell–intrinsic pathways directly blunting T cell activation and recruitment. Activated β-catenin signaling leads to a reduction of CCL4 production. CCL4 recruits cross-presenting CD103⁺ DC that are critical for cross-priming CD8⁺ T cells. With the loss of this population from the TME, the cancer-immunity cycle is not initiated. Furthermore, these DC produce the T cell chemoattractant CXCL9 and 10, so there is also loss of T cell recruitment. Elevated COX1/2 activity produces immunosuppressive PGE₂ that can function in a number of different ways. Here PGE₂ is shown to blunt the recruitment and activity of NK cells, leading to a loss of CCL5 and XCL1, chemokines that attract CD103⁺ DC, which lead to loss of T cell priming and recruitment. Loss of p53 results in a reduction of chemokine production by senescent tumor cells, like CCL2, that recruit NK cells to the TME. Moreover, p53^−/− tumors also lack production of ligands and cytokines to activate NK cells. The net result is impairment of tumor clearance mediated by NK cells. Loss of PTEN perturbs tumor cell autophagy. Reduction of autophagic activity could abrogate effective T cell priming and is shown to enhance resistance to T cell killing. Oncogenic MYC signaling up-regulates CD47 and PD-L1 on tumor cells. CD47 acts as a “don’t eat me” signal, inhibiting phagocytosis by engaging SIRPα on APC, including macrophages, while PD-L1 inhibits T cell function by engaging PD-1 on T cells. Epigenetic remodeling, induced by the activity of methyltransferases DNMT1 and EZH2, suppresses the expression of T cell recruiting chemokines CXCL9 and CXCL10, leading to a reduction in T cell infiltration.