title: Type 17 CD8+ T cells display enhanced antitumor immunity.
abstract: Interleukin-17 (IL-17)-secreting CD8(+) T cells have been described, but they have not been thoroughly studied and they do not have a known role in cancer immunotherapy. We skewed CD8(+) T cells to secrete IL-17 through priming in Th17-polarizing conditions. IL-17-producing CD8(+) T cells demonstrated reduced expression of Eomes and diminished cytolytic differentiation in vitro. However, after adoptive transfer, these cells converted to interferon-gamma-producing effector cells and mediated regression of large, established tumors. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells. This report is the first description of a cancer therapy with IL-17-secreting CD8(+) T cells. These findings have implications for the improvement of CD8(+) T cell-based adoptive immunotherapy.
authors.affiliation: National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hinrichs
authors.forename: Andrew
authors.initials: A
authors.lastname: Kaiser
authors.forename: Chrystal M
authors.initials: CM
authors.lastname: Paulos
authors.forename: Lydie
authors.initials: L
authors.lastname: Cassard
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Perez
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.forename: Claudia
authors.initials: C
authors.lastname: Wrzesinski
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Borman
authors.forename: Pawel
authors.initials: P
authors.lastname: Muranski
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation; D045744:Cell Line, Tumor; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D055630:Receptors, NK Cell Lectin-Like / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D020381:Interleukin-17; D020395:Receptors, Interleukin-7; D055630:Receptors, NK Cell Lectin-Like; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma