Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin
Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:186 |
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| Enthalten in: |
Cell - 186(2023), 17 vom: 17. Aug., Seite 3686-3705.e32 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ruf, Benjamin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.08.2023 Date Revised 29.08.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2023.07.026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360943624 |
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| 100 | 1 | |a Ruf, Benjamin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin |
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| 500 | |a Date Revised 29.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CODEX | |
| 650 | 4 | |a HCC | |
| 650 | 4 | |a MAIT cells | |
| 650 | 4 | |a S(3)-CIMA | |
| 650 | 4 | |a aPD-1/aPD-L1 | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a innate-like T cells | |
| 650 | 4 | |a mucosal-associated invariant T cells | |
| 650 | 4 | |a tumor immune microenvironment | |
| 650 | 4 | |a tumor-associated macrophages | |
| 700 | 1 | |a Bruhns, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Babaei, Sepideh |e verfasserin |4 aut | |
| 700 | 1 | |a Kedei, Noemi |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Lichun |e verfasserin |4 aut | |
| 700 | 1 | |a Revsine, Mahler |e verfasserin |4 aut | |
| 700 | 1 | |a Benmebarek, Mohamed-Reda |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Heinrich, Bernd |e verfasserin |4 aut | |
| 700 | 1 | |a Subramanyam, Varun |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Wabitsch, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Benjamin L |e verfasserin |4 aut | |
| 700 | 1 | |a Bauer, Kylynda C |e verfasserin |4 aut | |
| 700 | 1 | |a Myojin, Yuta |e verfasserin |4 aut | |
| 700 | 1 | |a Greten, Layla T |e verfasserin |4 aut | |
| 700 | 1 | |a McCallen, Justin D |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Trehan, Rajiv |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Nur, Amran |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy Soika, Dana Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Pouzolles, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Christine N |e verfasserin |4 aut | |
| 700 | 1 | |a Chari, Raj |e verfasserin |4 aut | |
| 700 | 1 | |a Kleiner, David E |e verfasserin |4 aut | |
| 700 | 1 | |a Telford, William |e verfasserin |4 aut | |
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| 700 | 1 | |a Ruchinskas, Allison |e verfasserin |4 aut | |
| 700 | 1 | |a Stovroff, Merrill K |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Jiman |e verfasserin |4 aut | |
| 700 | 1 | |a Oza, Kesha |e verfasserin |4 aut | |
| 700 | 1 | |a Ruchirawat, Mathuros |e verfasserin |4 aut | |
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| 700 | 1 | |a Korangy, Firouzeh |e verfasserin |4 aut | |
| 700 | 1 | |a Greten, Tim F |e verfasserin |4 aut | |
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