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The roles of PD-L1 in the various stages of tumor metastasis

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Abstract

The interaction between tumor programmed death ligand 1 (PD-L1) and T-cell programmed cell death 1 (PD-1) has long been acknowledged as a mechanism for evading immune surveillance. Recent studies, however, have unveiled a more nuanced role of tumor-intrinsic PD-L1 in reprograming tumoral phenotypes. Preclinical models emphasize the synchronized effects of both intracellular and extracellular PD-L1 in promoting metastasis, with intricate interactions with the immune system. This review aims to summarize recent findings to elucidate the spatiotemporal heterogeneity of PD-L1 expression and the pro-metastatic roles of PD-L1 in the entire process of tumor metastasis. For example, PD-L1 regulates the epithelial-to-mesenchymal transition (EMT) process, facilitates the survival of circulating tumor cells, and induces the formation of immunosuppressive environments at pre-metastatic niches and metastatic sites. And the complexed and dynamic regulation process of PD-L1 for tumor metastasis is related to the spatiotemporal heterogeneity of PD-L1 expression and functions from tumor primary sites to various metastatic sites. This review extends the current understandings for the roles of PD-L1 in mediating tumor metastasis and provides new insights into therapeutic decisions in clinical practice.

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Acknowledgements

All the figures were created with BioRender.com.

Funding

The work was supported by the National Natural Science Foundation of China (82173223, 82072629) and CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-044).

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  1. Yinjun He, Ming Zhu and Xuan Lai contributed equally to this work.

Authors and Affiliations

  1. Department of Colorectal Surgery, First Affiliated Hospital, Zhejiang University Medical School, Hangzhou, 310009, China

    Yinjun He & Weiqin Jiang

  2. Department of Pathology, Zhejiang University Medical School, Hangzhou, 310058, China

    Yinjun He, Ming Zhu, Xuan Lai, Honghe Zhang & Weiqin Jiang

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HZ and WJ Concepted and designed this review.YH, MZ and XL wrote the main manuscript text. YH prepared figures 1-4 and Ming Zhu prepared the table 1. HZ and WJ edited the manuscript. All authors reviewed the manuscript.

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Correspondence to Honghe Zhang or Weiqin Jiang.

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He, Y., Zhu, M., Lai, X. et al. The roles of PD-L1 in the various stages of tumor metastasis. Cancer Metastasis Rev (2024). https://doi.org/10.1007/s10555-024-10189-4

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