Multiomic analysis of malignant ascites defines RORC -expressing dendritic cells at sites of metastasis
Authors: Steven Michael Blum, Thomas L. Chan, Neal Patrick Smith, C T Ambrose, Katherine H. Xu, Alice J. Tirard, Nandini Samanta, Sidney Martin, Roya Best, Elizabeth Tuttle, Christopher T. Stueber, Yuhui Song, Vaishnavi Reddy Yalala, Haley Barnes, Sean T. Bannon, Chloe Simms, Benjamin Y. Arnold, Mushriq Al‐Jazrawe, Joseph Jonathan Zhao, Kamil Slowikowski, Jessica Tantivit, Kasidet Manakongtreecheep, Lukas M. Altenburger, Simon Knott, Matthew R. Strickland, Michael G. Drage, Linda T. Nieman, Jesse S. Boehm, Raghav Sundar, Gary Reynolds, Samuel Jacob Klempner, Alexandra–Chloé Villani
Journal: Science Immunology
Publication year: 2026
DOI: 10.1126/sciimmunol.aeb9068
Abstract
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.