While PRC2 can both directly and indirectly modulate cytokine signaling (Zingg et al., 2017, Abou El et al., 2015, Canadas et al., 2018), our findings suggest that H3K27me3 modification of MHC-I APP genes plays a critical role in maintaining MHC-I repression in cancer cells. The gene discussed is APP; the disease is cancer.