Abstract
Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs.
Highlights
Programmed cell death ligand 1 (PD-L1) is a 40 kDa transmembrane protein expressed by various activated immune cells and different non-lymphoid tissues [1,2]
Population: patients and pre-clinical models included in studies investigating the role of PD-L1 in prostate cancer (PC); Intervention: any treatment; Comparison: none; Outcomes: patient’s status at last follow-up, response to therapy, overall survival (OS), progression-free survival (PFS), biochemical recurrence-free survival (BCRFS), metastasis-free, cancer-specific, disease-free, or clinical failure-free survival
EpCAM+ circulating tumor cells (CTCs) compared to plasma-derived exosomes (PD-L1: 34/62, 54.8% vs. 15/62, 24.2%)
Summary
Programmed cell death ligand 1 (PD-L1) is a 40 kDa transmembrane protein expressed by various activated immune cells (such as macrophages, dendritic, NK, or B cells) and different non-lymphoid tissues (including epithelial, endothelial, or muscle cells) [1,2]. It binds to its receptor PD-1, which is expressed by cytotoxic T, B, NK cells, and monocytes. The PD-1/PD-L1 interaction serves as an important regulatory checkpoint against an excessive adaptive immune response to antigens and autoimmunity, playing a key role in immune regulation and peripheral tolerance [1,2]. PD-L1 is involved in the immune evasion process by tumor cells, including prostate cancer (PC) cells [1,2]. The 2021 United States National Comprehensive Cancer Network (NCCN) guidelines have allowed the use of pembrolizumab (an anti-PD-1 monoclonal antibody) in selected PC patients [4]
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