期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms21197139
关键词
immune checkpoint blockade; immunotherapy response biomarker; PD-L1 immune checkpoint; PD-L1 regulation; tumor microenvironment
资金
- Macquarie University
- Melanoma Institute Australia
- National Health and Medical Research Council of Australia (NHMRC) [10930, 1130423, 1093017]
- NHMRC Senior Research Fellowship
- National Health and Medical Research Council of Australia [1130423] Funding Source: NHMRC
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.
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