Laminin γ2-mediating T cell exclusion attenuates response to anti-PD-1 therapy
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 γ2 (Ln-γ2) predicted the attenuated efficacy of anti-PD-1 drugs and was...
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| Veröffentlicht in: | Science advances 2021-02, Vol.7 (6) |
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| creator | Li, Lei Wei, Jia-Ru Dong, Jun Lin, Qing-Guang Tang, Hong Jia, Yong-Xu Tan, Wanlin Chen, Qing-Yun Zeng, Ting-Ting Xing, Shan Qin, Yan-Ru Zhu, Ying-Hui Li, Yan Guan, Xin-Yuan |
| description | 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 γ2 (Ln-γ2) 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-γ2 was transcriptionally activated by transforming growth factor-β1 (TGF-β1) 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-β receptor inhibitor galunisertib and chemotherapy drugs provoked vigorous antitumor activity of anti-PD-1 therapy in mouse tumor models. Therefore, Ln-γ2 may represent a useful biomarker to optimize clinical decisions and predict the response of cancer patients to treatment with anti-PD-1 drugs. |
| doi_str_mv | 10.1126/sciadv.abc8346 |
| format | Article |
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Here, the up-regulation of laminin γ2 (Ln-γ2) 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-γ2 was transcriptionally activated by transforming growth factor-β1 (TGF-β1) 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-β receptor inhibitor galunisertib and chemotherapy drugs provoked vigorous antitumor activity of anti-PD-1 therapy in mouse tumor models. 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| subjects | Health and Medicine SciAdv r-articles |
| title | Laminin γ2-mediating T cell exclusion attenuates response to anti-PD-1 therapy |
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