Interleukin-17 inhibits tumor cell growth by means of a T-cell–dependent mechanism

• Published in: Blood Vol. 99; no. 6; pp. 2114 - 2121
• Main Authors: Benchetrit, Fabrice, Ciree, Arnaud, Vives, Virginie, Warnier, Guy, Gey, Alain, Sautès-Fridman, Catherine, Fossiez, François, Haicheur, Nacilla, Fridman, Wolf H., Tartour, Eric
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-03-2002; The Americain Society of Hematology
• Subjects: Animals; Antigens, Neoplasm - immunology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cancer Vaccines - pharmacology; Cell Division - drug effects; Female; Genetic Therapy - methods; Hematologic and hematopoietic diseases; Interleukin-17 - administration & dosage; Interleukin-17 - genetics; Interleukin-17 - pharmacology; Medical sciences; Mice; Mice, Nude; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - therapy; Platelet diseases and coagulopathies; Survival Rate; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Transfection; Treatment Outcome; Cell proliferation; Tumor cell; Interleukin 17; Mechanism; T-Lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.6.2114

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.