Abstract
The use of monoclonal antibodies targeting PD-1/PD-L1 axis completely changed anticancer treatment strategies. However, despite the significant improvement in overall survival and progression-free survival of patients undergoing these immunotherapy treatments, the only clinically accepted biomarker with some prediction capabilities for the outcome of the treatment is PD-L1 expression in tumor biopsies. Nevertheless, even when having PD-L1-positive tumors, numerous patients do not respond to these treatments. Considering the high cost of these therapies and the risk of immune-related adverse events during therapy, it is necessary to identify additional biomarkers that would facilitate stratifying patients in potential responders and non-responders before the start of immunotherapies. Here, we review the utility of PD-L1 expression not only in tumor cells but in immune system cells and their influence on the antitumor activity of immune cell subsets.
Highlights
Immune checkpoint inhibition (ICI) using monoclonal antibodies targeting the PD-1/PD-L1 axis are currently approved by the FDA for clinical use, with very good results in terms of improved progression-free survival (PFS) and overall survival (OS) in a variety of cancer types, including melanoma, lung, head and neck cancer and, invasive urothelial carcinoma
The authors propose the expression of PD-L1 on circulating T cells as a predictive biomarker of response to anti-CTLA4 immunotherapy, it has been argued by Brochez et al that the correlation of PD-L1+ lymphocytes with the clinical outcome is mainly related to the existence of a negative immune context characterized by the presence of Myeloid-derived suppressor cells (MDSCs) and Treg, and decreased plasmacytoid DCs (pDCs), rather than to the contribution of that particular population to the effect of immunotherapy [105]
Considering all the studies published by numerous authors in murine models as well as in clinical studies, PD-L1 expression on different non-tumor cell types, including several immune cell subsets, conditions the availability of T cells with effector activities that can respond to stimulation by ICIs
Summary
Immune checkpoint inhibition (ICI) using monoclonal antibodies targeting the PD-1/PD-L1 axis are currently approved by the FDA for clinical use, with very good results in terms of improved progression-free survival (PFS) and overall survival (OS) in a variety of cancer types, including melanoma, lung, head and neck cancer and, invasive urothelial carcinoma. The dynamic regulation of PD-L1 expression could explain clinical cases showing that patients diagnosed as tumor PD-L1 negative show objective responses to atezolizumab (an anti-PD-L1 antibody) as a second-line treatment [21]. Another concern is the heterogeneous nature of tumor, that may affect the PD-L1 quantification depending on the origin of the biopsy (primary tumor or metastasis), the degree of intratumoral heterogeneity and the sampling methodology (biopsy or tumor resection) [22].
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