Details

Autor(en) / Beteiligte

• Banerjee, Hridesh
• Nieves-Rosado, Hector
• Kulkarni, Aditi
• Murter, Benjamin
• McGrath, Kyle V.
• Chandran, Uma R.
• Chang, Alexander
• Szymczak-Workman, Andrea L.
• Vujanovic, Lazar
• Delgoffe, Greg M.
• Ferris, Robert L.
• Kane, Lawrence P.

Titel

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

Ist Teil von

• Cell reports (Cambridge), 2021-09, Vol.36 (11), p.109699-109699, Article 109699

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Treg cells expressing Tim-3 display a more activated phenotype•Enforced Treg cell expression of Tim-3 increases activated T cell frequency•Enforced expression of Tim-3 on Treg cells impairs T cell responses to tumors•Deletion of Tim-3 specifically from Treg cells improves anti-tumor T cell responses 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.