Laminin γ2-mediating T cell exclusion attenuates response to anti-PD-1 therapy

被引：67

作者：

Li, Lei ^{[1
,2
,3
,4
]}

Wei, Jia-Ru ^{[5
]}

Dong, Jun ^{[1
,2
]}

Lin, Qing-Guang ^{[1
,2
]}

Tang, Hong ^{[6
]}

Jia, Yong-Xu ^{[7
]}

Tan, Wanlin ^{[1
,2
]}

Chen, Qing-Yun ^{[1
,2
]}

Zeng, Ting-Ting ^{[1
,2
]}

Xing, Shan ^{[1
,2
]}

Qin, Yan-Ru ^{[7
]}

Zhu, Ying-Hui ^{[1
,2
]}

Li, Yan ^{[1
,2
]}

Guan, Xin-Yuan ^{[1
,2
,3
,4
,7
]}

机构：

[1] Sun Yat Sen Univ, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Peoples R China

[2] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Canc Ctr, Guangzhou 510060, Peoples R China

[3] Univ Hong Kong, Dept Clin Oncol, Hong Kong 00852, Peoples R China

[4] Univ Hongkong, Shenzhen Hosp, Dept Clin Oncol Ctr, Shenzhen 518058, Peoples R China

[5] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China

[6] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Dept Internal Med, Zhengzhou 450008, Peoples R China

[7] Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Oncol, Zhengzhou 450052, Peoples R China

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 06期

基金：

中国国家自然科学基金; 美国国家科学基金会;

关键词：

D O I：

10.1126/sciadv.abc8346

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

PD-1/PD-L1 blockade therapies provide notable clinical benefits for patients with advanced cancers, but the factors influencing the effectiveness of the treatment remain incompletely cataloged. Here, the up-regulation of laminin gamma 2 (Ln-gamma 2) predicted the attenuated efficacy of anti-PD-1 drugs and was associated with unfavorable outcomes in patients with lung cancer or esophageal cancer. Furthermore, Ln-gamma 2 was transcriptionally activated by transforming growth factor-beta 1 (TGF-beta 1) secreted from cancer-associated fibroblasts via JNK/AP1 signaling, which blocked T cell infiltration into the tumor nests by altering the expression of T cell receptors. Coadministration of the TGF-beta receptor inhibitor galunisertib and chemotherapy drugs provoked vigorous antitumor activity of anti-PD-1 therapy in mouse tumor models. Therefore, Ln-gamma 2 may represent a useful biomarker to optimize clinical decisions and predict the response of cancer patients to treatment with anti-PD-1 drugs.

引用

页数：14

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