Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy.
Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy.
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DOI：
10.1084/jem.20100269
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发表时间：
2011-03-14
期刊：
影响因子：
--
通讯作者：
Zitvogel L
中科院分区：
文献类型：
--
作者：
Ma Y;Aymeric L;Locher C;Mattarollo SR;Delahaye NF;Pereira P;Boucontet L;Apetoh L;Ghiringhelli F;Casares N;Lasarte JJ;Matsuzaki G;Ikuta K;Ryffel B;Benlagha K;Tesnière A;Ibrahim N;Déchanet-Merville J;Chaput N;Smyth MJ;Kroemer G;Zitvogel L
γδ T细胞产生IL-17是产生IFN-γ的CD8+ T细胞浸润肿瘤细胞和抑制肿瘤生长对蒽环类药物反应所必需的。通过触发免疫原性细胞死亡，一些抗癌化合物，包括蒽环类药物和奥沙利铂，引发肿瘤特异性的，产生干扰素γ的CD8+ αβ T淋巴细胞（Tc1 ctl），这是最佳治疗结果的关键。在这里，我们证明了化疗诱导产生白细胞介素(IL)-17的γδ (v γ γ4+和v γ γ6+) T淋巴细胞（γδ T17细胞）在肿瘤床内积累Tc1 ctl之前的快速和显著的入侵。在T细胞受体δ−/−或Vγ4/6−/−小鼠中，化疗的治疗效果受到影响，肿瘤浸润T细胞不产生IL-17， Tc1 ctl治疗后不能侵入肿瘤。虽然γδ T17细胞可以产生IL-17A和IL-22，但在四种独立的可移植肿瘤模型中，缺乏功能性IL-17A - il - 17r通路可显著降低肿瘤细胞死亡引起的肿瘤特异性T细胞反应，并降低化疗的疗效。γδ T细胞过继转移可恢复IL-17A−/−宿主的化疗效果。当输注的γδ T细胞缺乏IL-1R1或IL-17A时，其抗癌作用丧失。常规辅助性CD4+ αβ T细胞在化疗后不能产生IL-17。我们认为，γδ T17细胞在化疗诱导的抗癌免疫反应中起决定性作用。
IL-17 production by γδ T cells is required for tumor cell infiltration by IFN-γ–producing CD8+ T cells and inhibition of tumor growth in response to anthracyclines. 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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影响因子：
11.2
作者：
Dieli F;Vermijlen D;Fulfaro F;Caccamo N;Meraviglia S;Cicero G;Roberts A;Buccheri S;D'Asaro M;Gebbia N;Salerno A;Eberl M;Hayday AC
通讯作者：
Hayday AC
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
8
作者：
Maniati, E.;Soper, R.;Hagemann, T.
通讯作者：
Hagemann, T.
影响因子：
6.5
作者：
Kwong, Bernice Y.;Roberts, Scott J.;Girardi, Michael
通讯作者：
Girardi, Michael
DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G