Type 17 CD8+ T cells display enhanced antitumor immunity

Blood. 2009 Jul 16;114(3):596-9. doi: 10.1182/blood-2009-02-203935. Epub 2009 May 26.

Abstract

Interleukin-17 (IL-17)-secreting CD8(+) T cells have been described, but they have not been thoroughly studied and they do not have a known role in cancer immunotherapy. We skewed CD8(+) T cells to secrete IL-17 through priming in Th17-polarizing conditions. IL-17-producing CD8(+) T cells demonstrated reduced expression of Eomes and diminished cytolytic differentiation in vitro. However, after adoptive transfer, these cells converted to interferon-gamma-producing effector cells and mediated regression of large, established tumors. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells. This report is the first description of a cancer therapy with IL-17-secreting CD8(+) T cells. These findings have implications for the improvement of CD8(+) T cell-based adoptive immunotherapy.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Line, Tumor
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Transgenic
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, NK Cell Lectin-Like / biosynthesis
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Interleukin-17
  • Receptors, Interleukin-7
  • Receptors, NK Cell Lectin-Like
  • interleukin-7 receptor, alpha chain
  • Interferon-gamma