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 articlepeer-review

    17 Citations (Scopus)
    4 Downloads (Pure)

    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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