| Autor: |
Hridesh Banerjee, Hector Nieves-Rosado, Aditi Kulkarni, Benjamin Murter, Kyle V. McGrath, Uma R. Chandran, Alexander Chang, Andrea L. Szymczak-Workman, Lazar Vujanovic, Greg M. Delgoffe, Robert L. Ferris, Lawrence P. Kane |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 36, Iss 11, Pp 109699- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2021.109699 |
| Popis: |
Summary: Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3+ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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