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Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin.
Ruf, Benjamin; Bruhns, Matthias; Babaei, Sepideh; Kedei, Noemi; Ma, Lichun; Revsine, Mahler; Benmebarek, Mohamed-Reda; Ma, Chi; Heinrich, Bernd; Subramanyam, Varun; Qi, Jonathan; Wabitsch, Simon; Green, Benjamin L; Bauer, Kylynda C; Myojin, Yuta; Greten, Layla T; McCallen, Justin D; Huang, Patrick; Trehan, Rajiv; Wang, Xin; Nur, Amran; Murphy Soika, Dana Qiang; Pouzolles, Marie; Evans, Christine N; Chari, Raj; Kleiner, David E; Telford, William; Dadkhah, Kimia; Ruchinskas, Allison; Stovroff, Merrill K; Kang, Jiman; Oza, Kesha; Ruchirawat, Mathuros; Kroemer, Alexander; Wang, Xin Wei; Claassen, Manfred; Korangy, Firouzeh; Greten, Tim F.
Afiliación
  • 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
  • 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, U
  • 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
  • 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.gre
Cell ; 186(17): 3686-3705.e32, 2023 08 17.
Article en En | MEDLINE | ID: mdl-37595566
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Células T Invariantes Asociadas a Mucosa / Neoplasias Hepáticas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Células T Invariantes Asociadas a Mucosa / Neoplasias Hepáticas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cell Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos