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Article Dans Une Revue OncoImmunology Année : 2020

IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 + T-cell responses

Résumé

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.
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Dates et versions

hal-03100073 , version 1 (06-01-2021)

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Paternité - Pas d'utilisation commerciale

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Gilles Dadaglio, Catherine Fayolle, Marine Oberkampf, Alexandre Tang, Francesc Rudilla, et al.. IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 + T-cell responses. OncoImmunology, 2020, 9 (1), pp.1758606. ⟨10.1080/2162402X.2020.1758606⟩. ⟨hal-03100073⟩
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