What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy

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.

Repurposing of the antibiotic nitroxoline for the treatment of mpox

“…Moreover, inhibitors of PI3K/AKT/mTOR (buparlisib, LY294002, PI-103) and MAPK (sorafenib, regorafenib) signalling inhibited mpox virus infection (Figure 3G,H). These data agree with previous findings showing that nitroxoline inhibits PI3K/AKT/mTOR and Raf/MEK/ERK signalling [Chang et al, 2015; Xu et al, 2019; Palicelli et al, 2021] and that orthopoxvirus replication critically depends on PI3K/AKT/mTOR and Raf/MEK/ERK signalling [Kindrachuk et al, 2012; Beerli et al, 2019; Peng et al, 2020]. Taken together, these data suggest that nitroxoline inhibits mpox virus infection at least in part by interference with these two host cell signalling pathways.…”

“…Here, we investigated the antibiotic nitroxoline, which is used as a first-line therapy for uncomplicated urinary tract infections [Naber et al, 2014; Dobrindt et al, 2021; Wykowski et al, 2022], for activity against mpox viruses. Nitroxoline is known to inhibit the PI3K/AKT/mTOR and Raf/MEK/ERK signalling pathways [Chang et al, 2015; Xu et al, 2019; Palicelli et al, 2021], which are known to be critically involved in orthopoxvirus replication [Kindrachuk et al, 2012; Beerli et al, 2019; Peng et al, 2020]. As an antibiotic, nitroxoline also has the potential to target sexually transmitted bacteria that are commonly co-transmitted with mpox virus during the current outbreak and can aggravate mpox disease [Girometti et al, 2022; Hoffmann et al, 2022; Huang & Wang, 2022; Iñigo Martínez et al, 2022].…”

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, BRCA, PTEN, and Other Genes

“…To better present the data of our SLR, we have split the discussion of our results into different articles, highlighting relevant subtopics: PD-L1 IHC expression in PC with discussion of pre-analytical and interpretation variables; correlations of PD-L1 expression with clinic–pathological features in PC patients; PD-L1 intracellular signaling pathways in PC cells and regulation of the tumor microenvironment; pre-clinical models (cell lines, mouse models) and experimental treatments affecting PD-L1 expression in PC cells; genetic and epigenetic regulation of PD-L1; PD-L1 expression in liquid biopsies, etc. [ 260 , 261 , 262 , 263 , 264 , 265 ].…”

Cell membrane-coated human hair nanoparticles for precise disease therapies

“…IL-6 is a pro-inflammatory cytokine, and excessive IL-6 may reduce the production of perforin and granzyme, thereby mediating impaired NK cell function [41]. Literature has shown that IL-6 can inhibit the immune-killing ability of NK cells to tumors by activating the JAK/STAT3 pathway, thereby promoting tumor progression [42,43]. Although IL-12 is a proinflammatory factor, due to its pro-inflammatory and immunomodulatory abilities, it can induce tumors to change from "cold" to "hot" [44].…”