Spatial and temporal changes in PD-L1 expression in cancer

the role of genetic drivers, tumor microenvironment and resistance to therapy

Elena Shklovskaya*, Helen Rizos

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Immunotherapies blocking immune inhibitory receptors programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on T-cells have dramatically improved patient outcomes in a range of advanced cancers. However, the lack of response, and the development of resistance remain major obstacles to long-term improvements in patient outcomes. There is significant interest in the clinical use of biomarkers to improve patient selection, and the expression of PD-1 ligand 1 (PD-L1) is often reported as a potential biomarker of response. However, accumulating evidence suggests that the predictive value of PD-L1 expression in tumor biopsies is relatively low due, in part, to its complex biology. In this review, we discuss the biological consequences of PD-L1 expression by various cell types within the tumor microenvironment, and the complex mechanisms that regulate PD-L1 expression at the genomic, transcriptomic and proteomic levels.

Original languageEnglish
Article number7139
Pages (from-to)1-23
Number of pages23
JournalInternational Journal of Molecular Sciences
Volume21
Issue number19
DOIs
Publication statusPublished - 1 Oct 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Immune checkpoint blockade
  • Immunotherapy response biomarker
  • PD-L1 immune checkpoint
  • PD-L1 regulation
  • Tumor microenvironment

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