title: 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.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1102, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hamaï
authors.forename: Pascale
authors.initials: P
authors.lastname: Pignon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raimbaud
authors.forename: Karine
authors.initials: K
authors.lastname: Duperrier-Amouriaux
authors.forename: Hélène
authors.initials: H
authors.lastname: Senellart
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hiret
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D020381:Interleukin-17; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma