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 þ ) response to the important tumor antigen MAGE-A3, which occurred concurrently with a T H 1 (IFN-g þ ) response in a lung cancer patient. MAGE-A3-specific interleukin (IL)-17 þ T cells were mainly CCR7 þ central memory T cells, whereas IFN-g þ cells were enriched for CCR7 À effector

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... ory T cells. An assessment of the fine specificity of antigen recognition by these T cells indicated that the CCR6 þ CCR4 þ and CCR6 þ CXCR3 þ fractions contained the same T H 17/T H 1 population at early and late differentiation stages, respectively, whereas the CCR6 À CXCR3 þ fraction contained a distinct T H 1 population. These findings are important because they suggest a differentiation model in which tumor antigen-specific CD4 þ T cells that are primed under T H 17 polarizing conditions will progressively convert into IFN-g-secreting cells in vivo as they differentiate into effector T cells that can effectively attack tumors. Cancer Res; 72(5);