Skip NavigationSkip to Content
Return Return to Search Results

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

  1. Author:
    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

  2. Author Address

    Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Department of Internal Medicine I (Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics), University Hospital T 252;bingen, T 252;bingen, Germany; Department of Computer Science, University of T 252;bingen, T 252;bingen, Germany; University of T 252;bingen, Interfaculty Institute for Biomedical Informatics (IBMI), T 252;bingen, Germany; M3 Research Center, University Hospital T 252;bingen, T 252;bingen, Germany., Department of Internal Medicine I (Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectious Diseases and Geriatrics), University Hospital T 252;bingen, T 252;bingen, Germany; University of T 252;bingen, Interfaculty Institute for Biomedical Informatics (IBMI), T 252;bingen, Germany; M3 Research Center, University Hospital T 252;bingen, T 252;bingen, Germany., Collaborative Protein Technology Resource, OSTR, Office of the Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Laboratory of Human Carcinogenesis, Center for Cancer Research, National Institutes of Health, National Cancer Institute, Bethesda, MD, USA., 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., Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Genome Modification Core, Frederick National Lab for Cancer Research, Frederick, MD, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD, USA., MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, USA., 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., 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., 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.,
    1. Year: 2023
    2. Date: Aug 17
  2. Journal: Cell
    1. 186
    2. 17
    3. Pages: 3686-3705.e32
  4. Type of Article: Article
  1. 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. Published by Elsevier Inc.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2023.07.026
  3. PMID: 37595566
  4. PII : S0092-8674(23)00804-8

Library Notes

  1. Fiscal Year: FY2022-2023
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel