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


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
Issue number19
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.


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

Fingerprint Dive into the research topics of 'Spatial and temporal changes in PD-L1 expression in cancer: the role of genetic drivers, tumor microenvironment and resistance to therapy'. Together they form a unique fingerprint.

  • Projects

    Determinants of response to immune checkpoint inhibitors in melanoma

    Rizos, H., Long, G., Menzies, A. M., Yang, J., Carlino, M., Kefford, R., Scolyer, R., MQRES, M., MQRES 3 (International), M. 3. & De St Groth, B. F.


    Project: Research

    Molecular determinants of risk, progression and treatment response in melanoma

    Kefford, R., Thompson, J., Hersey, P., Mann, G., Scolyer, R., Hayward, N. & Long, G.

    1/01/16 → …

    Project: Research

    Cite this