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.

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.