Overview

The PD-1/PD-L1 immune checkpoint plays an important role in serving immune escape for tumor cells. Tumor cells can bypass antitumor immunity by manipulating these immune checkpoints. In a research article from Frontier, the authors commented that immunotherapy targeting on PD1/PDL1 axis can effectively block its pro-tumor activity; however, only a subset of patients can show responses clinically, with most of the patients cannot benefit from the anti-PD1/PDL1 therapy.

Science Advances has recently published a research article discussing the role of laminin γ2 in anti-PD-1 therapy and its potential use as a biomarker.

Below are some highlights from the research article:

Role of transforming growth factor–β1 (TGF-β1) in tumor microenvironment

  • TGF-β1 is a cytokine that is responsible to regulate cell growth, proliferation, differentiation, and apoptosis.
  • In cancer, TGF-β1 promotes the epithelial-mesenchymal transition (EMT) of tumor cells, angiogenesis, and metastasis.
  • TGF-β1 plays a crucial role in immune suppression within the tumor microenvironment.
  • A high level of TGF-β1 in the tumor microenvironment advances T cell exclusion and reduces the sensibility of tumors to anti–PD-1/PD-L1 therapies; however, further studies will be needed on its underlying mechanism.

Role of Laminin γ2 (Ln-γ2) and TGF-β in anti-PD-1 therapy

  • Ln-γ2 was triggered by TGF-β, which is secreted from the cancer-associated fibroblasts via JNK/AP1 signaling.
  • The up-regulation of Ln-γ2 predicted the reduced efficacy of anti–PD-1 drugs.
  • In mouse tumor models, application of the TGF-β receptor inhibitor provoked powerful antitumor activity of anti–PD-1 therapy.
  • Ln-γ2 may serve as a useful biomarker to foresee the response of cancer treatment with anti–PD-1 drugs.

Reference:

1. Lei Li, Jia-Ru Wei, Jun Dong, Qing-Guang Lin, Hong Tang, Yong-Xu Jia, Wanlin Tan, Qing-Yun Chen, Ting-Ting Zeng, Shan Xing, Yan-Ru Qin, Ying-Hui Zhu, Yan Li, and Xin-Yuan Guan. Laminin γ2–mediating T cell exclusion attenuates response to anti–PD-1 therapy. Science Advances. 2021 Feb 3. doi: 10.1126/sciadv.abc8346

2. Lei Q, Wang D, Sun K, Wang L and Zhang Y. Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors. Front. Cell Dev. Biol. 8:672. 2020 Jul 21. doi: 10.3389/fcell.2020.00672

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