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

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 Th17promoting 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.

Multi-Tissue Characterization of GILZ Expression in Dendritic Cell Subsets at Steady State and in Inflammatory Contexts

“…In terms of functional consequences, we can hypothesize from previous works that GILZ downregulation in mig/resDC2 would favor Th17 CD4 T-cell priming while its increase in resDC1 would rather promote Treg expansion [20,21,24,29]. Together, this would compromise anti-tumor response efficiency [51,52]. The opposite regulation of GILZ in cDC1 and cDC2 from tumorbearing mice is of particular interest in view of its contribution in the control of anti-cancer therapy efficiency [23].…”

A promising self-nanoemulsifying adjuvant with plant-derived saponin D boosts immune response and exerts an anti-tumor effect

“…Overall, these data provide supporting evidence that IL-17 may play a dual role in human tumor immunity. Moreover, the activation of tumor-specific Th17 cells may promote the therapeutic efficacy of cancer vaccines ( 40 ). In our study, we found that CTL responses induced by the Th1/Th17 cellular response ( Figure 4 ) were also dependent on IFN-γ, and type I IFN signaling by CD8 + T cell responses induced by OVA/SND were stronger for IFN-γ and IL-17 than those induced in the other groups.…”

LncRNAs Target Ferroptosis-Related Genes and Impair Activation of CD4+ T Cell in Gastric Cancer

“…Thus, we suggest that the hub FRGs have the potential to be involved in CD4 + T cell activation, especially Th cells. The activated Th cells may promote antitumor immunity in GC ( Dadaglio et al, 2020 ). PSAT1 (phospholipid sterol acyltransferase 1) has been reported to be critically important for the transition from p-Pyr to p-Ser ( Mullarky et al, 2016 ) and further affects ferroptosis ( Zhang et al, 2019 ).…”