CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer.
CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer.
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CCL7招募cDC1促进抗肿瘤免疫并促进非小细胞肺癌的检查点免疫治疗
DOI：
10.1038/s41467-020-19973-6
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发表时间：
2020-11-30
影响因子：
16.6
通讯作者：
Zhong B
中科院分区：
文献类型：
--
作者：
Zhang M;Yang W;Wang P;Deng Y;Dong YT;Liu FF;Huang R;Zhang P;Duan YQ;Liu XD;Lin D;Chu Q;Zhong B
检查点免疫治疗对非小细胞肺癌（NSCLC）的疗效在很大程度上取决于肿瘤微环境（TME）。在这里，我们证明了CCL 7通过将常规DC 1（cDC 1）募集到TME中以促进T细胞扩增，促进KrasLSL − G12 D/+ Tp 53 fl/fl（KP）和KrasLSL− G12 D/+ Lkb 1fl/fl（KL）NSCLC小鼠模型的抗PD-1治疗。CCL 7在NSCLC肿瘤组织中表现出高表达，并且与TME中cDC 1的浸润和NSCLC患者的总生存率正相关。CCL 7缺乏削弱了TME中cDC 1的浸润以及随后支气管引流淋巴结和TME中CD 8+和CD 4 + T细胞的扩增，从而促进了KP小鼠模型中的肿瘤发展。CCL 7单独或与抗PD-1联合肺内给药可显著抑制肿瘤发展并延长KP和KL小鼠的生存期。提示CCL 7有可能作为NSCLC检查点免疫治疗的生物标志物和佐剂。只有有限比例的非小细胞肺癌患者对抗PD-1/PD-L1免疫治疗有反应。在这里，作者表明，在KRAS突变肺癌的本地模型中，CCL 7促进cDC 1浸润到肺部，维持抗肿瘤免疫应答并增强抗PD 1治疗效果。
The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL−G12D/+Tp53fl/fl (KP) and the KrasLSL−G12D/+Lkb1fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+ and CD4+ T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC. Only a limited proportion of patients with non-small cell lung cancer respond to anti-PD-1/PD-L1 immunotherapy. Here, the authors show that in autochthonous models of KRAS-mutated lung cancer, CCL7 promotes cDC1 infiltration into the lungs, sustaining antitumor immune responses and potentiating anti-PD1 treatment efficacy.
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影响因子：
50.3
作者：
Li F;Han X;Li F;Wang R;Wang H;Gao Y;Wang X;Fang Z;Zhang W;Yao S;Tong X;Wang Y;Feng Y;Sun Y;Li Y;Wong KK;Zhai Q;Chen H;Ji H
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DOI：
10.1073/pnas.1509968112
发表时间：
2015-09-08
影响因子：
11.1
作者：
Lin, Dandan;Zhang, Man;Zhong, Bo
通讯作者：
Zhong, Bo
影响因子：
64.8
作者：
Dou Z;Ghosh K;Vizioli MG;Zhu J;Sen P;Wangensteen KJ;Simithy J;Lan Y;Lin Y;Zhou Z;Capell BC;Xu C;Xu M;Kieckhaefer JE;Jiang T;Shoshkes-Carmel M;Tanim KMAA;Barber GN;Seykora JT;Millar SE;Kaestner KH;Garcia BA;Adams PD;Berger SL
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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