Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.

Yuting Ma (1, 2) , Laetitia Aymeric (1, 2) , Clara Locher (1, 2) , Stephen R Mattarollo (3) , Nicolas F Delahaye (1) , Pablo Pereira (4) , Laurent Boucontet (4) , Lionel Apetoh (5, 6) , François Ghiringhelli (5, 6) , Noëlia Casares (7) , Juan José Lasarte (7) , Goro Matsuzaki (8) , Koichi Ikuta (9) , Bernhard Ryffel (10) , Kamel Benlagha (11) , Antoine Tesnière (12) , Nicolas Ibrahim (13) , Julie Déchanet-Merville (14) , Nathalie Chaput (1, 15) , Mark J Smyth (3) , Guido Kroemer (12, 16, 17, 18, 19) , Laurence Zitvogel (1, 15, 20)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 Ecole doctorale de cancérologie
3 Cancer immunology program
4 Développement des Lymphocytes
5 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
6 LNC - Lipides - Nutrition - Cancer (U866)
7 CIMA - Division of Hepatology and Gene Therapy
8 COMB - Molecular Microbiology Group
9 Laboratory of Biological protection
10 IEM - Immunologie et Embryologie Moléculaires
11 UMR_S 561 - Immunologie, génétique et traitement des maladies métaboliques et du diabète
12 U848 - Apoptose, cancer et immunité
13 Département de biologie et pathologie médicales [Gustave Roussy]
14 CIRID - Composantes innées de la réponse immunitaire et différenciation
15 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
16 Plateforme de métabolomique
17 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
18 Pôle de biologie
19 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
20 School of Medicine

By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ-producing CD8(+) αβ T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17-producing γδ (Vγ4(+) and Vγ6(+)) T lymphocytes (γδ T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor δ(-/-) or Vγ4/6(-/-) mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although γδ T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A-IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of γδ T cells restored the efficacy of chemotherapy in IL-17A(-/-) hosts. The anticancer effect of infused γδ T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4(+) αβ T cells failed to produce IL-17 after chemotherapy. We conclude that γδ T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.

Domaines: Immunologie

Yuting Ma, Laetitia Aymeric, Clara Locher, Stephen R Mattarollo, Nicolas F Delahaye, et al.. Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.. Journal of Experimental Medicine, 2011, 208 (3), pp.491-503. ⟨10.1084/jem.20100269⟩. ⟨pasteur-00576679⟩