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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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
Descripción
Sumario: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.