Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic

Cancer Immunol Immunother. 2016 Mar;65(3):247-59. doi: 10.1007/s00262-016-1797-6. Epub 2016 Jan 29.

Abstract

Cancer immunotherapy is one the most effective approaches for treating patients with tumors, as it bolsters the generation and persistence of memory T cells. In preclinical work, it has been reported that adoptively transferred CD4+ and CD8+ lymphocytes that secrete IL-17A (i.e., Th17 and Tc17 cells) regress tumors to a greater extent than IFN-γ(+)Th1 or Tc1 cells in vivo. Herein, we review the mechanisms underlying how infused Th17 and Tc17 cells regress established malignancies in clinically relevant mouse models of cancer. We also discuss how unique signaling cues--such as co-stimulatory molecules (ICOS and 41BB), cytokines (IL-12 and IL-23) or pharmaceutical reagents (Akt inhibitors, etc.)--can be exploited to bolster the therapeutic potential of IL-17(+) lymphocytes with an emphasis on using this knowledge to improve next-generation clinical trials for patients with cancer.

Keywords: ACT; Cancer; Immunotherapy; Tc17; Th17.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Humans
  • Immunologic Memory
  • Immunotherapy
  • Inducible T-Cell Co-Stimulator Protein / physiology
  • Interleukin-12 / physiology
  • Interleukin-17 / biosynthesis*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / immunology
  • Th17 Cells / physiology

Substances

  • ICOS protein, human
  • IL17A protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-17
  • Interleukin-12