Human T(H)17 immune cells specific for the tumor antigen MAGE-A3 convert to IFN-γ-secreting cells as they differentiate into effector T cells in vivo

Cancer Res. 2012 Mar 1;72(5):1059-63. doi: 10.1158/0008-5472.CAN-11-3432. Epub 2012 Jan 17.

Abstract

The role of T(H)17 cells in cancer is being investigated, but the existence of tumor antigen-specific T(H)17 cells has yet to be ascertained. Here, we report the first description of a spontaneous T(H)17 (IL-17(+)) response to the important tumor antigen MAGE-A3, which occurred concurrently with a T(H)1 (IFN-γ(+)) response in a lung cancer patient. MAGE-A3-specific interleukin (IL)-17(+) T cells were mainly CCR7(+) central memory T cells, whereas IFN-γ(+) cells were enriched for CCR7(-) effector memory T cells. An assessment of the fine specificity of antigen recognition by these T cells indicated that the CCR6(+)CCR4(+) and CCR6(+)CXCR3(+) fractions contained the same T(H)17/T(H)1 population at early and late differentiation stages, respectively, whereas the CCR6(-)CXCR3(+) fraction contained a distinct T(H)1 population. These findings are important because they suggest a differentiation model in which tumor antigen-specific CD4(+) T cells that are primed under T(H)17 polarizing conditions will progressively convert into IFN-γ-secreting cells in vivo as they differentiate into effector T cells that can effectively attack tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Epitopes
  • Humans
  • Immunologic Memory
  • Interferon-gamma / metabolism*
  • Interleukin-17 / metabolism
  • Lung Neoplasms / immunology*
  • Neoplasm Proteins / immunology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology*

Substances

  • Antigens, Neoplasm
  • Epitopes
  • Interleukin-17
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Interferon-gamma