Oncogene-Expressing senescent melanocytes upregulate MHC Class II, re-localize to the lymph nodes and activate T cells

OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined. Here we show that engagement of OIS in primary human melanocytes, specifically by melanoma driver mutations NRASQ61K and BRAFV600E, causes expression of the MHC class II antigen presentation apparatus, via secreted IL1ß signaling and expression of CIITA, a master regulator of MHC class II gene transcription. Overall design: We quantify transcription via high throughput RNA sequencing in nevus melanocytes in cross FVB/NJ mice with Cre inducible NRAS61K with an MHCII cross

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van Tuyn J, Jaber-Hijazi F, MacKenzie D, Cole JJ, Mann E, Pawlikowski JS, Rai TS, Nelson DM, McBryan T, Ivanov A, Blyth K, Wu H, Milling S, Adams PD