Cell Reports (Sep 2021)

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

  • 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

Journal volume & issue
Vol. 36, no. 11
p. 109699

Abstract

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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.

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