Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors

Abstract

PD-1/PD-L1 axis represents an important target for renormalizing and resetting anti-tumor immunity in cancer patients. Currently, anti-PD-1/PD-L1 therapy has been applied in a broad spectrum of tumors and has yielded durable remission in patients. However, how to further broaden the application, guide personalized therapeutic strategies, and improve clinical responses remains a vital task. At present, PD-L1 expression is an important parameter of clinical indications for immune checkpoint blockade in many types of cancers, a strategy based on the supposition that positive PD-L1 expression reflects local T cell response. Recent studies have revealed that PD-L1 expression is regulated by multiple layers of complicated factors, during which the host immune microenvironment exerts a pivotal role and determines the clinical efficacy of the therapy. In this review, we will summarize recent findings on PD-1/PD-L1 in cancer, focusing on how local immune landscape participates in the regulation of PD-L1 expression and modification. Importantly, we will also discuss these topics in the context of clinical treatment and analyze how these fundamental principles might inspire our efforts to develop more precise and effective immune therapeutics for cancer.

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Acknowledgements

We sincerely apologize to the fellow researchers whose important work is not included in this paper. The presentation of a complete and extensive review is extremely challenging owing to the plethora of literature related to the topic. We apologize in advance for any inadvertent omission. This work was supported by project Grants from the National Key Research and Development Plan of China (2016YFA0502600 and 2018ZX10302205); the National Natural Science Foundation of China (31830025 and 81901585); the Natural Science Foundation of Guangdong Province, China (2018B030308010 and 2019A1515011770); the China Postdoctoral Science Foundation (2019M653191 and 2020T130738); and the Fundamental Research Funds for the Central Universities (19lgjc09 and 19lgpy167).

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Wei, Y., Xiao, X., Lao, X. et al. Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors. Cell. Mol. Life Sci. (2020). https://doi.org/10.1007/s00018-020-03637-1

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Keywords

  • PD-L1 expression
  • Immune microenvironment
  • Combinatorial immune checkpoint therapy
  • Metabolic reprogramming
  • Epigenetic reprogramming
  • Exosomal PD-L1