Type 17 CD8+ T cells display enhanced antitumor immunity.
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.
Hinrichs
Christian S
CS
National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Kaiser
Andrew
A
Paulos
Chrystal M
CM
Cassard
Lydie
L
Sanchez-Perez
Luis
L
Heemskerk
Bianca
B
Wrzesinski
Claudia
C
Borman
Zachary A
ZA
Muranski
Pawel
P
Restifo
Nicholas P
NP
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
D020381:Interleukin-17; D020395:Receptors, Interleukin-7; D055630:Receptors, NK Cell Lectin-Like; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma