A mosaic renal myeloid subtype linked to immune escape correlates with poor patient survival in clear cell renal cell carcinoma [ex vivo]

Mononuclear phagocytes moderate tissue repair, immune activation and tolerance. In the renal tubulo-interstitium, specialized DCs help maintain homeostasis and protect tubuli from immune injury. Human renal cell carcinoma is immunogenic; yet immunotherapies that target T-cell dysfunction show limited clinical efficacy suggesting additional mechanisms of immunoinhibition. We previously described “enriched-in-renal cell carcinoma” (erc)DCs. In tumor tissue, they are found in tight contact with T cells which are dysfunctional. Here we describe that ercDCs exhibit a distinct polarization state imparted by tissue-specific signals characteristic for ccRCC and renal tissue homeostasis. The resulting mosaic transcript signature includes features associated with host defense activity, angiogenesis/invasion and T-cell inhibition. An ercDC-specific profile was predictive for patient survival and suggests potential therapeutic targets for improved immunotherapy. RNA isolated from FACS-sorted donor cells.