IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses
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 u...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1758606 |
| _version_ | 1818821162372694016 |
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| author | Gilles Dadaglio Catherine Fayolle Marine Oberkampf Alexandre Tang Francesc Rudilla Isabelle Couillin Eirik A. Torheim Pierre Rosenbaum Claude Leclerc |
| author_facet | Gilles Dadaglio Catherine Fayolle Marine Oberkampf Alexandre Tang Francesc Rudilla Isabelle Couillin Eirik A. Torheim Pierre Rosenbaum Claude Leclerc |
| author_sort | Gilles Dadaglio |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T23:03:48Z |
| format | Article |
| id | doaj.art-5233de5bf6bf40c49d8d32de56bb46e2 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-18T23:03:48Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-5233de5bf6bf40c49d8d32de56bb46e22022-12-21T20:48:30ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17586061758606IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responsesGilles Dadaglio0Catherine Fayolle1Marine Oberkampf2Alexandre Tang3Francesc Rudilla4Isabelle Couillin5Eirik A. Torheim6Pierre Rosenbaum7Claude Leclerc8Unité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerNEM, CNRS, UMR7355 INEM, CNRS and University of OrléansUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerUnité de Régulation Immunitaire et Vaccinologie, Equipe Labellisée Ligue Contre le CancerAntitumor 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.http://dx.doi.org/10.1080/2162402X.2020.1758606tumor immunityth17 cellsil-17cytotoxic t cellsneutrophils |
| spellingShingle | Gilles Dadaglio Catherine Fayolle Marine Oberkampf Alexandre Tang Francesc Rudilla Isabelle Couillin Eirik A. Torheim Pierre Rosenbaum Claude Leclerc IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses OncoImmunology tumor immunity th17 cells il-17 cytotoxic t cells neutrophils |
| title | IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses |
| title_full | IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses |
| title_fullStr | IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses |
| title_full_unstemmed | IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses |
| title_short | IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8+ T-cell responses |
| title_sort | il 17 suppresses the therapeutic activity of cancer vaccines through the inhibition of cd8 t cell responses |
| topic | tumor immunity th17 cells il-17 cytotoxic t cells neutrophils |
| url | http://dx.doi.org/10.1080/2162402X.2020.1758606 |
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