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

Mol Cancer. 2019 Jan 15;18(1):10. doi: 10.1186/s12943-018-0928-4.

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.

Keywords: Inflammatory factor; PD-1; PD-L1; Tumor immune escape; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen / immunology*
  • Humans
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • Tumor Escape / immunology*
  • Tumor Microenvironment / immunology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor