Contribution of IL-17–producing γδ T cells to the efficacy of anticancer chemotherapy
Contribution of IL-17–producing γδ T cells to the efficacy of anticancer chemotherapy
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DOI：
10.1084/jem.201002692084c
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发表时间：
2011-04-11
期刊：
影响因子：
--
通讯作者：
Zitvogel L
中科院分区：
文献类型：
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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
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）可引发肿瘤特异性、产生干扰素-γ的CD 8 +αβ T淋巴细胞（Tc 1 CTL），这对于获得最佳治疗结局至关重要。在这里，我们证明化疗诱导产生白细胞介素（IL）-17（Vγ4+和Vγ6+）的γδ T淋巴细胞（γδ T17细胞）快速而显著的侵袭，这先于肿瘤床内Tc 1 CTL的积累。在T细胞受体δ−/−或Vγ4/6−/−小鼠中，化疗的治疗效果受到损害，肿瘤浸润性T细胞不产生IL-17，治疗后Tc 1 CTL未能侵入肿瘤。尽管γδ T17细胞可以产生IL-17 A和IL-22，但功能性IL-17 A-IL-17 R通路的缺乏显著降低了由肿瘤细胞死亡引起的肿瘤特异性T细胞应答，以及四种独立的可移植肿瘤模型中化疗的功效。γδ T细胞的连续转移恢复了IL-17 A −/−宿主中化疗的疗效。当输注的γδ T细胞缺乏IL-1 R1或IL-17 A时，其抗癌作用丧失。常规辅助性CD 4 +αβ T细胞在化疗后不能产生IL-17。我们得出结论，γδ T17细胞在化疗诱导的抗癌免疫应答中起决定性作用。
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.
DOI：
10.1084/jem.20100269
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
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
通讯作者：
Zitvogel L