| First Author | Ruf B | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 17 | Pages | 3686-3705.e32 |
| PubMed ID | 37595566 | Mgi Jnum | J:339307 |
| Mgi Id | MGI:7521870 | Doi | 10.1016/j.cell.2023.07.026 |
| Citation | Ruf B, et al. (2023) Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin. Cell 186(17):3686-3705.e32 |
| abstractText | 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. |
