What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3166 - 3166

Published: Nov. 14, 2021

Immunotherapy targeting the PD-1-PD-L1 axis yielded good results in treating different immunologically ''hot'' tumors. A phase II study revealed therapeutic activity of pembrolizumab selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes immunohistochemical expression PD-L1 human PC samples and highlights pre-analytical interpretation variables. Interestingly, 29% acinar PCs, 7% ductal 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria applied variable specimen-types, evaluating tumors showing clinic-pathologic features. The positivity rate antibody clones tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding single case tested for RM-320. most clone was E1L3N, followed by 22C3 (most used eligibility), SP263, SP142, 28-8, gave rates 35%, 11-41% (depending systems), 6%, 3%, 15%, respectively. Other <200 cases. usually higher than benign tissues. It non-tissue microarray specimens (41-50% vs. 15%), as frequently showed heterogenous focal PD-L1-staining. expressed immune stromal 12% 69% cases, Tumor heterogeneity, inter-institutional preanalytics, inter-observer variability may account result biases.

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12330 - 12330

Published: Nov. 15, 2021

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in cells. TME influences the survival/progression of prostate cancer (PC), enabling cell immune-evasion also through activation PD-1/PD-L1 axis. We have performed a systematic literature review according to PRISMA guidelines, investigate how pathway is influenced by ISPs. Tumor immune-escape mechanisms include suppression/exhaustion infiltrating cytotoxic T lymphocytes, inhibition suppressive NK increase immune-suppressive cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, other soluble molecules secreted components (and sometimes increased patients' serum), as well hypoxia, regulation PD-L1. Experimental studies using human mouse PC lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that ERK/MEK, Akt-mTOR, NF-kB, WNT JAK/STAT were involved PD-L1 upregulation PC. Blocking immunotherapy drugs can prevent immune-escape, increasing anti-tumor activity

Language: Английский

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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

Biomedicines, Journal Year: 2022, Volume and Issue: 10(2), P. 236 - 236

Published: Jan. 22, 2022

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR).

Language: Английский

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Prognostic significance of soluble PD-L1 in prostate cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 11, 2024

Purpose The aim of this study was to assess the role sPD-L1 and sPD-1 as potential biomarkers in prostate cancer (PCa). association values these soluble proteins were correlated clinical data: stage disease, Gleason score, biochemical recurrence etc. For a comprehensive study, relationship between circulating immune cells further investigated. Methods A total 88 patients with pT2 pT3 PCa diagnosis 41 heathy men enrolled. Soluble levels measured plasma by ELISA method. Immunophenotyping performed flow cytometry analysis. Results Our study’s findings demonstrate that had higher comparing healthy controls (p &lt; 0.001). We found statistically significant 0.05) improved progression free survival lower initial values. Furthermore, sPD-1/sPD-L1 ratio associated probability disease 0.05). Additionally, discovered scores elevated preoperative advanced strong correlation 0.05), immunosuppressive CD4+CD25+FoxP3+ regulatory T baseline observed unfavorable postoperative course supporting idea elements influence each other progression. In addition drop PD-L1, inverse percentage M-MDSC BCR suggests is not source patients. Conclusion suggest promising prognostic marker cancer.

Language: Английский

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Ancestry-Specific DNA Damage Repair Gene Mutations and Prostate Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 682 - 682

Published: Feb. 18, 2025

This review is intended to reflect the currently available literature on both clinically significant germline mutations in DNA damage repair (DDR) genes as well importance of ancestral diversity pathogenesis prostate cancer (PCa). The second most prevalent worldwide men PCa, causing morbidity and mortality its advanced stage. Emerging data highlight substantial role DDR PCa pathogenesis, especially progression aggressive forms disease. Germline genetic testing recognized a necessary tool for efficient, individualized patient care. NCCR guidelines recommend inquiring about family history known variants and, if indicated, proceeding with multigene followed by post-test counseling. Depending HR or MMR genes, specific treatment options may provide clinical benefit. We will discuss that are involved prognosis racially diverse populations.

Language: Английский

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PD-L1 expression in prostate cancer and Gleason Grade Group: is there any relationship? Findings from a multi-institutional cohort.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155916 - 155916

Published: March 1, 2025

Language: Английский

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PD - L1 (SP263) expression correlates with pathological aggressive parameters in prostate cancer

Annals of Diagnostic Pathology, Journal Year: 2025, Volume and Issue: 78, P. 152481 - 152481

Published: April 12, 2025

Language: Английский

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Challenges and the Evolving Landscape of Assessing Blood-Based PD-L1 Expression as a Biomarker for Anti-PD-(L)1 Immunotherapy

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1181 - 1181

Published: May 20, 2022

While promising, PD-L1 expression on tumor tissues as assessed by immunohistochemistry has been shown to be an imperfect biomarker that only applies a limited number of cancers, whereas many patients with PD-L1-negative tumors still respond anti-PD-(L)1 immunotherapy. Recent studies using patient blood samples assess immunotherapeutic responsiveness suggests promising approach the identification novel and/or improved biomarkers for In this review, we discuss advances in our evolving understanding regulation and function expression, which is foundation developing blood-based We further current knowledge clinical study results immune cells, exosomes, soluble forms peripheral blood. Finally, key challenges successful development potential use

Language: Английский

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What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models)

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(22), P. 12297 - 12297

Published: Nov. 14, 2021

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating effects of treatments (alone or combined) may discover how to overcome immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) delineate landscape pre-clinical (including cell lines mouse models) that tested with on PD-L1 PC. NF-kB, MEK, JAK, STAT inhibitors human/mouse, primary/metastatic PC-cell variably down-modulated PD-L1-expression, reducing chemoresistance tumor migration. If PC-cells were co-cultured NK, CD8+ T-cells CAR-T cells, immune cytotoxicity increased when was downregulated (opposite for upregulation). models, radiotherapy, CDK4/6-inhibitors, RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs reduce expression. some PC blocking only pathway had limited efficacy growth. Anti-tumor could be combining blockade other approaches (inhibitors tyrosine kinase, PI3K/mTOR JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).

Language: Английский

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A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(6), P. 1016 - 1016

Published: June 19, 2023

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like (SRCC) a very rare PA subtype, with around 200 cases reported English literature. Histologically, tumor cells show vacuole compressing nucleus to periphery. Pagetoid spread acini and ducts usually related metastases from urothelial or colorectal carcinomas, less commonly associated intraductal carcinoma (IC); histologically, grow between acinar secretory basal cell layers. To our knowledge, we report first prostatic SRCC (Gleason score 10, stage pT3b) IC pagetoid seminal vesicles. systematic literature review (PRISMA guidelines), it tested case for both PD-L1 (<1% of positive cells, clone 22C3) mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no previously MMR, while only four previous showed high expression another (28-8). Finally, discussed differential diagnoses SRCC.

Language: Английский

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