Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin.

Autor:	Ruf B; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Bruhns M; Department of Internal Medicine I (Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics), University Hospital Tübingen, Tübingen, Germany; Department of Computer Science, University of Tübingen, Tübingen, Germany; University of Tübingen, Interfaculty Institute for Biomedical Informatics (IBMI), Tübingen, Germany; M3 Research Center, University Hospital Tübingen, Tübingen, Germany., Babaei S; Department of Internal Medicine I (Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics), University Hospital Tübingen, Tübingen, Germany; University of Tübingen, Interfaculty Institute for Biomedical Informatics (IBMI), Tübingen, Germany; M3 Research Center, University Hospital Tübingen, Tübingen, Germany., Kedei N; Collaborative Protein Technology Resource, OSTR, Office of the Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Ma L; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA., Revsine M; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA., Benmebarek MR; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Ma C; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Heinrich B; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Subramanyam V; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Qi J; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Wabitsch S; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Surgery, Medical University of Vienna, Vienna, Austria., Green BL; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Bauer KC; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Myojin Y; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Greten LT; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., McCallen JD; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Huang P; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Trehan R; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Wang X; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Nur A; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Murphy Soika DQ; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Pouzolles M; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Evans CN; Genome Modification Core, Frederick National Lab for Cancer Research, Frederick, MD, USA., Chari R; Genome Modification Core, Frederick National Lab for Cancer Research, Frederick, MD, USA., Kleiner DE; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Telford W; Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Dadkhah K; Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD, USA., Ruchinskas A; Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD, USA., Stovroff MK; MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA., Kang J; MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA., Oza K; MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA., Ruchirawat M; Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, Thailand; Center of Excellence on Environmental Health and Toxicology, Office of the Higher Education Commission, Ministry of Education, Bangkok, Thailand., Kroemer A; MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA., Wang XW; Laboratory of Human Carcinogenesis, Center for Cancer Research, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA; NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA., Claassen M; Department of Internal Medicine I (Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics), University Hospital Tübingen, Tübingen, Germany; Department of Computer Science, University of Tübingen, Tübingen, Germany; University of Tübingen, Interfaculty Institute for Biomedical Informatics (IBMI), Tübingen, Germany; M3 Research Center, University Hospital Tübingen, Tübingen, Germany., Korangy F; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Greten TF; Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA. Electronic address: tim.greten@nih.gov.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 Aug 17; Vol. 186 (17), pp. 3686-3705.e32.
DOI:	10.1016/j.cell.2023.07.026
Abstrakt:	Mucosal-associated invariant T (MAIT) cells represent an abundant innate-like T cell subtype in the human liver. MAIT cells are assigned crucial roles in regulating immunity and inflammation, yet their role in liver cancer remains elusive. Here, we present a MAIT cell-centered profiling of hepatocellular carcinoma (HCC) using scRNA-seq, flow cytometry, and co-detection by indexing (CODEX) imaging of paired patient samples. These analyses highlight the heterogeneity and dysfunctionality of MAIT cells in HCC and their defective capacity to infiltrate liver tumors. Machine-learning tools were used to dissect the spatial cellular interaction network within the MAIT cell neighborhood. Co-localization in the adjacent liver and interaction between niche-occupying CSF1R + PD-L1 + tumor-associated macrophages (TAMs) and MAIT cells was identified as a key regulatory element of MAIT cell dysfunction. Perturbation of this cell-cell interaction in ex vivo co-culture studies using patient samples and murine models reinvigorated MAIT cell cytotoxicity. These studies suggest that aPD-1/aPD-L1 therapies target MAIT cells in HCC patients. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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