These changes in the composition of the secretome (e.g., overexpression of MMP3, which cleaves activating MICA ligands from the senescent cell surface, or HLA-E-, an inhibitory ligand that blocks NK cell killing) can lead to a redirection of macrophage polarization from a tumor-inhibiting M1 state to a tumor-promoting M2 state that prevents the elimination of senescence-escaped cancer cells [124,130,131]. The gene discussed is HLA-E; the disease is neoplasm.