IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 + T-cell responses
| Autor: | Marine Oberkampf, Alexandre Tang, Eirik A Torheim, Pierre Rosenbaum, Gilles Dadaglio, Claude Leclerc, Francesc Rudilla, Catherine Fayolle, Isabelle Couillin |
|---|---|
| Přispěvatelé: | Couillin, Isabelle, Régulation Immunitaire et Vaccinologie, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Ligue Contre le Cancer, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment [SDV]Life Sciences [q-bio] Immunology Melanoma Experimental [SDV.CAN]Life Sciences [q-bio]/Cancer CD8-Positive T-Lymphocytes Cancer Vaccines Mice 03 medical and health sciences 0302 clinical medicine [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology Adjuvants Immunologic neutrophils [SDV.CAN] Life Sciences [q-bio]/Cancer Immunity Neoplasms Tumor immunity medicine Animals Immunology and Allergy Cytotoxic T cell Th17 cells RC254-282 Original Research Chemistry cytotoxic T cells Interleukin-17 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunotherapy Th1 Cells RC581-607 3. Good health Mice Inbred C57BL [SDV] Life Sciences [q-bio] CTL Cytolysis IL-17 030104 developmental biology Oncology 030220 oncology & carcinogenesis Systemic administration Cancer research Female Interleukin 17 Immunologic diseases. Allergy [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology CD8 Research Article |
| Zdroj: | OncoImmunology OncoImmunology, 2020, 9 (1), pp.1758606. ⟨10.1080/2162402X.2020.1758606⟩ OncoImmunology, Vol 9, Iss 1 (2020) Oncoimmunology article-version (VoR) Version of Record OncoImmunology, Taylor & Francis, 2020, 9 (1), pp.1758606. ⟨10.1080/2162402X.2020.1758606⟩ |
| ISSN: | 2162-4011 2162-402X |
| DOI: | 10.1080/2162402X.2020.1758606⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|