Predictive and Prognostic Role of PD-L1 in Urothelial Carcinoma Patients with Anti-PD-1/PD-L1 Therapy: A Systematic Review and Meta-Analysis

Liu, Haoran; Ye, Tao; Yang, Xiaoqi; Lv, Ping; Wu, Xiaoliang; Zhou, Hui; Lu, Huiqi; Tang, Kun; Ye, Zhangqun

doi:10.1155/2020/8375348

Cited by 15 publications

(6 citation statements)

References 41 publications

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“…Interestingly, the predictive value of PD-L1 expression significantly decreased in patients receiving anti-PD-L1 agents compared to those receiving anti-PD-1 agents. This trend has also been observed in carcinomas other than BTC (17,56,57). Further studies are warranted to verify whether the predictive value of PD-L1 expression differs depending on the target of ICIs (PD-1 vs. PD-L1) in cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 68%

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis

Yoon,

Woo,

Chun

et al. 2024

Front. Immunol.

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BackgroundRecently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy.MethodsWe conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.ResultsA total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression.ConclusionPD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

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Section: Discussionmentioning

confidence: 68%

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis

Yoon,

Woo,

Chun

et al. 2024

Front. Immunol.

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“…In a separate analysis of patients with 1 of 10 prespecified advanced rare tumor types previously conducted through the Aarhus University pathology network, the prevalence of PD-L1 positivity varied from 13% in patients with neuroendocrine tumors (n=30) to 86% in patients with vulvar carcinoma (n=44) (26). Variation in prevalence of PD-L1 expression has also been reported in studies evaluating other tumor types, including NSCLC (25), gastric cancer (27)(28)(29), urothelial cancer (30), triple-negative breast cancer (31), and cervical carcinoma (32). Additionally, the relationship between PD-L1 positivity and clinical outcomes has also been found to vary between tumor types (29,(31)(32)(33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 71%

Molecular epidemiology study of programmed death ligand 1 and ligand 2 protein expression assessed by immunohistochemistry in extensive-stage small-cell lung cancer

Steiniche,

Georgsen,

Meldgaard

et al. 2024

Front. Oncol.

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ObjectivesPrevalence of tumor PD-L1 expression in extensive-stage small-cell lung cancer (ES-SCLC) is variable, and data on PD-L2 expression are limited. The prognostic values of these biomarkers are not well understood. The current study was conducted to address these data gaps.MethodsA retrospective cohort study of Danish patients with histologically confirmed ES-SCLC and evaluable tumor samples who were receiving usual care before the introduction of immunotherapy was conducted. Protein expression of PD-L1 and PD-L2 was determined by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx assay and a PD-L2 IHC assay using a propriety mouse monoclonal antibody. A combined positive score (CPS) of ≥1 was used to define biomarker positivity. Kaplan-Meier plots and Cox proportional hazard models were employed to assess the relationship between PD-L1 and PD-L2 protein expression and OS.ResultsAmong 80 patients, 31% (n=25) and 36% (n=29) had disease positive for PD-L1 and PD-L2, respectively. Overall, 85% (n=68) of patients had concordant PD-L1/PD-L2 status; 26% (n=21) had double positive disease (both PD-L1 and PD-L2 CPS ≥1) and 59% (n=47) had double negative disease (both PD-L1 and PD-L2 CPS <1). PD-L1 and PD-L2 positivity were each associated with longer OS (unadjusted hazard ratios [HRs], 0.35 [95% CI, 0.21−0.61] and 0.50 [95% CI, 0.31−0.82]); the associations persisted after adjustment for several known prognostic factors (HRs, 0.41 [95% CI, 0.22–0.75] and 0.44 [95% CI, 0.25–0.79] for PD-L1 and PD-L2 positivity, respectively). When evaluating OS in patients with double positive disease, unadjusted and adjusted HRs for double positive compared with double negative were similar to those with only PD-L1 or PD-L2 positivity (unadjusted HR, 0.36 [95% CI, 0.20–0.64]; adjusted HR, 0.36 [0.18−0.73]).ConclusionPD-L1 and PD-L2 positivity were observed in approximately one-third of assessed ES-SCLC tumor samples and were highly congruent. Patients with PD-L1 and PD-L2 positivity, alone or combined, were associated with longer OS, independent of other prognostic factors.

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“…17,18 Measurements of PD-L1 have been evaluated as a putative biomarker to inform the response to ICIs, but levels of expression are not always correlated with clinical responses. 19 Different studies found that between 14% and 29% of WT show tumor upregulation of PD-L1. [20][21][22] Zhang et al showed PD-L1 expression in 29% of 77 primary WT tumors, and 35% in metastatic WT.…”

Section: The Tumor Microenvironment In Wilms Tumormentioning

confidence: 99%

“…One of the most studied inhibitory pathways involves PD‐L1 and PD‐L2, B7 family members and ligands for the inhibitory receptor PD‐1 expressed by activated T cells 17,18 . Measurements of PD‐L1 have been evaluated as a putative biomarker to inform the response to ICIs, but levels of expression are not always correlated with clinical responses 19 . Different studies found that between 14% and 29% of WT show tumor upregulation of PD‐L1 20–22 .…”

Section: The Tumor Microenvironment In Wilms Tumormentioning

confidence: 99%

The tumor microenvironment and immune targeting therapy in pediatric renal tumors

Hont

Dumont

Sutton

et al. 2022

Pediatric Blood & Cancer

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This review highlights the role of several immunomodulating elements contributing to the tumor microenvironment of various pediatric renal tumors including Wilms tumor.The roles of innate and adaptive immune cells in renal tumors are summarized as well as immunomodulatory cytokines and other proteins. The expression and the predictive role of checkpoint modulators like PD-L1 and immunomodulating proteins like glypican-3, B7-H3, COX-2 are highlighted with a translational view toward potential therapeutic innovations. We further discuss the current state of preclinical models in advancing this field of study. Finally, examples of clinical trials of immunomodulating strategies such as monoclonal antibodies and chimeric antigen receptor T (CAR-T) cells for relapsed/refractory/progressive pediatric renal tumors are described.

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Predictive and Prognostic Role of PD-L1 in Urothelial Carcinoma Patients with Anti-PD-1/PD-L1 Therapy: A Systematic Review and Meta-Analysis

Cited by 15 publications

References 41 publications

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis

Molecular epidemiology study of programmed death ligand 1 and ligand 2 protein expression assessed by immunohistochemistry in extensive-stage small-cell lung cancer

The tumor microenvironment and immune targeting therapy in pediatric renal tumors

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