| First Author | Yu L | Year | 2023 |
| Journal | Int J Cancer | Volume | 153 |
| Issue | 9 | Pages | 1684-1697 |
| PubMed ID | 37531161 | Mgi Jnum | J:341103 |
| Mgi Id | MGI:7531928 | Doi | 10.1002/ijc.34669 |
| Citation | Yu L, et al. (2023) Tumor-infiltrating gamma delta T-cells reveal exhausted subsets with remarkable heterogeneity in colorectal cancer. Int J Cancer 153(9):1684-1697 |
| abstractText | The gammadeltaT-cells recognize infected or transformed cells. However, unlike alphabetaT-cells, gammadeltaT-cells are innate-like immune cells, with no major histocompatibility complex restriction requirements. gammadeltaT-cells are the main population of intestinal intraepithelial lymphocytes (IELs) and are associated with the antitumor immune response, particularly in colorectal cancer (CRC). Although CD8(+) T-cells exhibit dysfunction and even exhaustion in the tumor microenvironment (TME), which contributes to tumor immune escape, whether the same applies to tumor-infiltrating (TI)-gammadeltaT-cells is not completely understood. Here, we sought to investigate the expression pattern of inhibitory receptors and functional state of TI-gammadeltaT-cells, and reveal the features of exhausted TI-gammadeltaT-cells in the CRC TME. We demonstrated that TI-gammadeltaT-cells exhibited exhaustion phenotypes and displayed more severe functional exhaustion than TI-CD8(+) T-cells or NK-cells in the TME of CRC. In addition, scRNA-seq analysis of TI-gammadeltaT-cells revealed three exhausted subsets with remarkable heterogeneity. The presence of three heterogeneous exhausted gammadeltaT-cell (Tex) populations, including Tex(prog) , Tex(tran) and Tex(term) were further confirmed by flow cytometry, on the basis of PD-1 and TIM-3 expression. Finally, we revealed that c-Maf not only contributed to gammadeltaT-cell exhaustion via upregulation of inhibitory receptors, but also involved in the exhaustion of CD8(+) T and NK-cells. c-Maf may also be an important contributor to gammadeltaT-cell exhaustion in CRC patients. These findings indicated that TI-gammadeltaT-cells exhibit phenotypic and functional exhaustion in the CRC TME. The revealed features of exhausted TI-gammadeltaT-cells may provide help for understanding the mechanisms and the association of gammadeltaT-cell exhaustion with tumor development and pathogenesis. |
