Multiomic analysis of malignant ascites defines RORC-expressing dendritic cells at sites of metastasis.

Malignant ascites is caused by the peritoneal dissemination of cancer and has a poor prognosis. Here, we performed multiomic analyses on ascites samples from patients with cancer and identified RORC-expressing dendritic cells (RORC DCs) enriched in malignant ascites. RORC DCs expressed PIGR and were transcriptionally similar to murine RORγt+ DCs/Thetis cells implicated in immune tolerance. We devised a high-purity sorting strategy to enable in vitro experiments with patient-derived RORC DCs, which indicated that these cells were phenotypically stable and stimulated T cell proliferation while attenuating IFNG expression. Multiplexed immunofluorescence identified RORC DCs in primary tumors and demonstrated their enrichment in regional lymph node metastases. These results associate human RORC DCs with advanced malignancies and suggest a role for these cells in the tumor microenvironment.