Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism.
Interleukin 17 (IL-17) is a proinflammatory cytokine produced by activated CD4(+) memory T cells. We previously showed that IL-17 increased the growth rate of human cervical tumors transplanted into athymic nude mice. To address the possible role of T cells in the biologic activity of IL-17 for tumor control, we grafted 2 murine hematopoietic immunogenic tumors (P815 and J558L) transfected with a complementary DNA encoding murine IL-17 into syngeneic immunocompetent mice. We found that growth of the 2 IL-17-producing tumors was significantly inhibited compared with that of mock-transfected tumors. In contrast to the antitumor activity of IL-17 observed in immunocompetent mice, we observed no difference in the in vivo growth of IL-17-transfected or mock-transfected P815 cells (P815-IL-17 and P815-Neo, respectively) transplanted into nude mice. We then showed that IL-17 increased generation of specific cytolytic T lymphocytes (CTLs) directed against the immunodominant antigens from P815 called A, B, C, D, and E, since all mice injected with P815-IL-17 developed a P815-specific CTL response, whereas only 6 of 16 mice immunized with P815-Neo had a specific CTL response against the antigens. The induction of CTLs was associated with establishment of a tumor-protective immunity. These experiments suggest that T lymphocytes are involved in the antitumor activity of IL-17. Therefore, IL-17, like other cytokines, appears to be a pleiotropic cytokine with possible protumor or antitumor effects on tumor development, which often depends on the immunogenicity of tumor models.
Benchetrit
Fabrice
F
INSERM U 255, Université Pierre et Marie Curie, Hopital Européen Georges Pompidou, 20 Rue Leblanc, 75908 Paris Cedex 15, France.
Ciree
Arnaud
A
Vives
Virginie
V
Warnier
Guy
G
Gey
Alain
A
Sautès-Fridman
Catherine
C
Fossiez
François
F
Haicheur
Nacilla
N
Fridman
Wolf H
WH
Tartour
Eric
E
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D019496:Cancer Vaccines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D020381:Interleukin-17 / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014162:Transfection; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D020381:Interleukin-17