IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses.
Oncoimmunology
; 9(1): 1758606, 2020 05 12.
Article
en En
| MEDLINE
| ID: mdl-32923117
ABSTRACT
Antitumor immunity is mediated by Th1 CD4+ and CD8+ T lymphocytes, which induce tumor-specific cytolysis, whereas Th17 CD4+ T cells have been described to promote tumor growth. Here, we explored the influence of IL-17 on the ability of therapeutic vaccines to induce the rejection of tumors in mice using several adjuvants known to elicit either Th1 or Th17-type immunity. Immunization of mice with Th1-adjuvanted vaccine induced high levels of IFN-γ-producing T cells, whereas injection with Th17-promoting adjuvants triggered the stimulation of both IL-17 and IFN-γ-producing T cells. However, despite their capacity to induce strong Th1 responses, these Th17-promoting adjuvants failed to induce the eradication of tumors. In addition, the systemic administration of IL-17A strongly decreases the therapeutic effect of Th1-adjuvanted vaccines in two different tumor models. This suppressive effect correlated with the capacity of systemically delivered IL-17A to inhibit the induction of CD8+ T-cell responses. The suppressive effect of IL-17A on the induction of CD8+ T-cell responses was abolished in mice depleted of neutrophils, clearly demonstrating the role played by these cells in the inhibitory effect of IL-17A in the induction of antitumor responses. These results demonstrate that even though strong Th1-type responses favor tumor control, the simultaneous activation of Th17 cells may redirect or curtail tumor-specific immunity through a mechanism involving neutrophils. This study establishes that IL-17 plays a detrimental role in the development of an effective antitumor T cell response and thus could strongly affect the efficiency of immunotherapy through the inhibition of CTL responses.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD8-positivos
/
Vacunas contra el Cáncer
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Interleucina-17
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Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Oncoimmunology
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia