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

Yuting Ma; Laetitia Aymeric; Clara Locher; Stephen R Mattarollo; Nicolas F Delahaye; Pablo Pereira; Laurent Boucontet; Lionel Apetoh; François Ghiringhelli; Noëlia Casares; Juan José Lasarte; Goro Matsuzaki; Koichi Ikuta; Bernhard Ryffel; Kamel Benlagha; Antoine Tesnière; Nicolas Ibrahim; Julie Déchanet-Merville; Nathalie Chaput; Mark J Smyth; Guido Kroemer; Laurence Zitvogel

doi:10.1084/jem.20100269

Journal articles

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, *}

* Corresponding author

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

Direction de la recherche [Gustave Roussy]

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

Abstract : 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.

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Journal articles

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Life Sciences [q-bio] / Immunology

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

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

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