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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857690/ https://www.ncbi.nlm.nih.gov/pubmed/33536206 http://dx.doi.org/10.1126/sciadv.abc8346 |
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author | 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 |
author_facet | 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 |
author_sort | Li, Lei |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7857690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78576902021-02-16 Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy 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 Sci Adv Research Articles 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. American Association for the Advancement of Science 2021-02-03 /pmc/articles/PMC7857690/ /pubmed/33536206 http://dx.doi.org/10.1126/sciadv.abc8346 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles 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 Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title | Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title_full | Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title_fullStr | Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title_full_unstemmed | Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title_short | Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy |
title_sort | laminin γ2–mediating t cell exclusion attenuates response to anti–pd-1 therapy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857690/ https://www.ncbi.nlm.nih.gov/pubmed/33536206 http://dx.doi.org/10.1126/sciadv.abc8346 |
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