Mechanisms controlling PD-L1 expression in cancer

By Jong-Ho Cha, Li-Chuan Chan, Chia‐Wei Li, J. Hsu, M. Hung. Molecules and Cells, 2019

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The engagement of programmed cell death protein 1 (PD-1; encoded by the PDCD1 gene) receptor expressed on activated T cells and its ligand programmed death-ligand 1 (PD-L1; encoded by the CD274 gene) is a major co-inhibitory checkpoint signaling that controls T-cell activities. Various types of cancers express high levels of PD-L1 and exploit the PD-L1/PD-1 signaling to evade T-cell immunity. Blocking the PD-L1/PD-1 pathway has consistently shown remarkable anti-tumor effects in patients with advanced cancers and is recognized as the gold standard for developing new immune checkpoint blockade (ICB) and combination therapies. However, the response rates of anti-PD-L1 have been limited in several solid tumors. Therefore, furthering our understanding of the regulatory mechanisms of PD-L1 can bring substantial benefits to patients with cancers by improving the efficacy of current PD-L1/PD-1 blockade or other ICBs. In this review article, we provide current knowledge of PD-L1 regulatory mechanisms at the transcriptional, posttranscriptional, post-translational, and extracellular level, and discuss the implications of these findings in cancer diagnosis and immunotherapy.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/8f241791837d9401cae03806657d99ae2ecbea91