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

IF 16.4 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2026-10-02 DOI:10.1126/sciimmunol.aeb9068

Steven M. Blum, Thomas L. Chan, Neal P. Smith, Courtney Ambrose, Katherine H. Xu, Alice Tirard, Nandini Samanta, Sidney Martin, Roya Best, Elizabeth Tuttle, Christopher T. Stueber, Yuhui Song, Vaishnavi R. Yalala, Haley Barnes, Sean T. Bannon, Chloe Simms, Benjamin Y. Arnold, Mushriq Al-Jazrawe, Joseph J. 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 J. Klempner, Alexandra-Chloé Villani

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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.

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恶性腹水的多组学分析确定了在转移部位表达RORC的树突状细胞

恶性腹水是由肿瘤向腹膜扩散引起的，预后较差。在这里，我们对来自癌症患者的腹水样本进行了多组学分析，并鉴定了在恶性腹水中富集表达RORC的树突状细胞（RORC dc）。RORC dc表达PIGR，并且在转录上与小鼠RORγt + dc /Thetis细胞相似，与免疫耐受有关。我们设计了一种高纯度的分选策略，以便对患者来源的RORC dc进行体外实验，结果表明，这些细胞在表型上是稳定的，并在抑制IFNG表达的同时刺激T细胞增殖。多重免疫荧光鉴定了原发肿瘤中的RORC dc，并证实其在区域淋巴结转移中富集。这些结果将人类RORC dc与晚期恶性肿瘤联系起来，并提示这些细胞在肿瘤微环境中的作用。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.