Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment
| Autor: | Lazar Vujanovic, Lawrence P. Kane, Aditi Kulkarni, Andrea L. Szymczak-Workman, Hector Nieves-Rosado, Benjamin Murter, Robert L. Ferris, Kyle V. McGrath, Greg M. Delgoffe, Hridesh Banerjee, Alexander Chang, Uma R. Chandran |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cell signaling Cell type QH301-705.5 Programmed Cell Death 1 Receptor Melanoma Experimental Mice Transgenic chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Biology T-Lymphocytes Regulatory Article Oxidative Phosphorylation General Biochemistry Genetics and Molecular Biology Mice Immunity Tumor Microenvironment Animals tumor immunology Biology (General) Hepatitis A Virus Cellular Receptor 2 Tumor microenvironment immunosuppression Effector TOR Serine-Threonine Kinases regulatory T cells (Treg) hemic and immune systems Phenotype T cell immunoglobulin and mucin 3 (Tim-3) Interleukin-10 Cell biology Mice Inbred C57BL Lymphatic system Gene Expression Regulation Female cellular signaling Glycolysis Homeostasis cellular metabolism Signal Transduction |
| Zdroj: | Cell Reports, Vol 36, Iss 11, Pp 109699-(2021) Cell reports |
| ISSN: | 2211-1247 |
| 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. In brief Regulatory T cells (Treg cells) limit the immune response to tumors, and tumor-infiltrating Treg cells are especially suppressive. However, the mechanisms underlying enhanced Treg cell function are poorly understood. Banerjee et al. show that Tim-3 expression is linked to increased Treg cell suppressive activity, possibly through the cytokine IL-10, in mouse models and people with cancer. Graphical Abstract |
| Databáze: | OpenAIRE |
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