Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.

Mol Cancer

NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.

Published: January 2019


Article Synopsis

  • Tumor immune escape is a key strategy for tumor survival, primarily achieved through immunosuppression mechanisms that inhibit T cell activation.
  • The PD-L1/PD-1 signaling pathway plays a critical role in this process by promoting immune tolerance in tumor cells, making it a target for cancer therapies.
  • Despite its potential, the effectiveness of PD-L1/PD-1 targeting remains limited, emphasizing the need for a better understanding of the molecular mechanisms regulating this pathway in the tumor microenvironment.

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Article Abstract

Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332843PMC
http://dx.doi.org/10.1186/s12943-018-0928-4DOI Listing

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