التفاصيل البيبلوغرافية
| العنوان: |
Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin. |
| المؤلفون: |
Ruf, Benjamin1 (AUTHOR), Bruhns, Matthias1,2,3,4,5 (AUTHOR), Babaei, Sepideh1,2,4,5 (AUTHOR), Kedei, Noemi6 (AUTHOR), Ma, Lichun7 (AUTHOR), Revsine, Mahler7 (AUTHOR), Benmebarek, Mohamed-Reda1 (AUTHOR), Ma, Chi1 (AUTHOR), Heinrich, Bernd1 (AUTHOR), Subramanyam, Varun1 (AUTHOR), Qi, Jonathan1 (AUTHOR), Wabitsch, Simon1,8 (AUTHOR), Green, Benjamin L.1 (AUTHOR), Bauer, Kylynda C.1 (AUTHOR), Myojin, Yuta1 (AUTHOR), Greten, Layla T.1 (AUTHOR), McCallen, Justin D.1 (AUTHOR), Huang, Patrick1 (AUTHOR), Trehan, Rajiv1 (AUTHOR), Wang, Xin1 (AUTHOR) |
| المصدر: |
Cell. Aug2023, Vol. 186 Issue 17, p3686-3686. 1p. |
| مصطلحات موضوعية: |
*CELL communication, *MACROPHAGES, *CELL physiology, *HEPATOCELLULAR carcinoma, *T cells, *MACHINE learning, *PROGRAMMED cell death 1 receptors |
| مستخلص: |
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. [Display omitted] • HCC patient sample profiles by flow cytometry, scRNA-seq, imaging, and machine learning • MAIT cells in HCC show impaired tumor infiltration, dysfunction, and loss of cytotoxicity • TAMs impact MAIT cell function through interaction at the tumor-to-liver interface • aPD-1/aPD-L1 directed therapies target MAIT cells in HCC Insights into the functions of an underappreciated type of immune cell, the mucosal-associated invariant T (MAIT) cell, and how the immunosuppressive tumor microenvironment restrains these cells, with potential implications for treating hepatocellular carcinoma with cancer immunotherapy. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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