Prognostic significance of programmed cell death‐ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta‐analysis

Ouyang, Yong; Liu, Wendao; Yang, Xiao; Li, Jinwei; Long, Shunqin

doi:10.1002/cam4.4236

Cited by 19 publications

(13 citation statements)

References 65 publications

(145 reference statements)

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“…Other studies have shown that PD-L1+ CTCs are associated with poor prognosis in NSCLC ( 39 , 43 - 45 ) and that PD-L1 expression increased at progression ( 46 ). However, in patients receiving immunotherapy, PD-L1 expression by CTC predicted better response to therapy ( 47 , 48 ). Furthermore, we have previously seen that CTCs are associated with abnormalities in peripheral blood immune cells ( 49 , 50 ) suggesting that further study is warranted.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer

Cohen¹,

Jayachandran²,

Gao³

et al. 2023

Transl Lung Cancer Res

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Background Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC. Methods CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase chain reaction (RT-PCR) using a customized pre-selected panel of 20 genes. Results At least 1 CTC was detected by enumeration in 53.8% of samples. Most patients had fewer than 5 CTCs (91%) and the highest observed count was 35 CTCs. Enumeration of single CTCs was not prognostic, although detection of CTC clusters at any time point was associated with increased risk of progression [hazard ratio (HR) 3.00, 95% confidence interval (CI): 1.1–8.2, P=0.0318]. In contrast, 124 (97.6%) patients with samples interrogated for gene expression had at least 1 gene detectable in at least 1 sample, and 101 (79.5%) had at least one elevated epithelial gene in at least one timepoint. High expression of BCL2, CD274 [programmed death-ligand 1 (PD-L1)], CDH1, EPCAM, FGFR1, FN1, KRT18, MET and MUC1 were associated with poor prognosis. Patients with CTCs positive for at least 3 epithelial genes at baseline all progressed within 10 months (HR 8.2, P<0.001, 95% CI: 3.2–21.1). BCL2, CD274 (PD-L1), EPCAM and MUC1 remained significant independent prognostic factors in multivariate, time-dependent analyses of progression and death. Conclusions The selective profile of CTC genes and identification of CTC clusters better correlated with prognosis than enumeration of enriched CTC in NSCLC patients in this study.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer

Cohen¹,

Jayachandran²,

Gao³

et al. 2023

Transl Lung Cancer Res

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“…On two occasions, the presence of PD-L1 + CTCs was associated with longer PFS and/or OS [ 34 , 41 ]. In a recent meta-analysis, the existence of PD-L1 + CTCs was not associated with PFS or OS; however, in ICI-treated patients, the presence of PD-L1 + CTCs predicted better survival compared to patients undergoing other therapies [ 44 ]. In our study, the presence of PD-L1 and, more specifically, the phenotype CK + PD-L1 + CD45 − at baseline and after one cycle of treatment demonstrated a trend towards lower PFS 12m (log-rank p = 0.073 and log-rank p = 0.094, respectively).…”

Section: Discussionmentioning

confidence: 99%

PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

et al. 2022

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The PD-1/PD-L1 axis provides CTCs an escape route from the immune system. Phosphorylation of the ribosomal protein S6 is implicated in the same pathway, following mTOR activation. The aim of the study was to investigate the expression of PD-L1 and pS6 in CTCs from NSCLC patients under Osimertinib treatment at a single cell level. CTCs were isolated using ISET from NSCLC patients’ blood [37 at baseline, 25 after the 1st cycle, and 23 at the end of treatment (EOT)]. Staining was performed using immunofluorescence. Cytokeratin-positive (CK+) CTCs were detected in 62% of patients. CK+PD-L1+CD45− and CK+pS6+ phenotypes were detected in 38% and 41% of the patients at baseline, in 28% and 32% after 1st cycle, and in 30% and 35% at EOT, respectively. Spearman’s analysis revealed statistically significant correlations between PD-L1 and pS6 phenotypes at all time points. Survival analysis revealed that CK+pS6+ (p = 0.003) and CKlowpS6+ (p = 0.021) phenotypes after 1st cycle were related to significantly decreased one-year progression-free survival (PFS12m) and PFS, respectively. CK+PD-L1+CD45−phenotype at baseline and after 1st cycle showed a trend for decreased PFS12m. Increased expression of PD-L1/pS6 in CTCs of Osimertinib-treated NSCLC patients implies the activation of the corresponding pathway, which is potentially associated with poor clinical outcomes.

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“…However, this conclusion requires prospective studies to evaluate the predictive value of PD-L1 expression in ES-SCLC immunotherapy. Circulating tumour cells (CTCs) are a “liquid biopsy specimen” that can replace the primary tumour ( 41 ). The expression of PD-L1 in CTCs can be used to evaluate the efficacy of PD-1/PD-L1 mAbs in non-small cell lung cancer patients ( 42 , 43 ).…”

Section: Discussionmentioning

confidence: 99%

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

et al. 2022

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ObjectivesTo provide an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) of the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of extensive-stage small-cell lung cancer (ES-SCLC).MethodsPubMed, Web of Science, Embase, Clinicaltrials and the Cochrane Library were systematically searched to extract RCTs concerning the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of ES-SCLC from the time of database inception to October 31, 2022. The literature was independently selected, information was extracted and the risk of bias of the RCTs was evaluated according to the inclusion and exclusion criteria. Stata14.0 was used for the meta-analysis.ResultsSix studies involving 2,600 patients were included in the analysis. The results of the meta-analysis showed that the combination of PD-1/PD-L1 inhibitors significantly improved the OS (HR: 0.73, 95% CI: 0.66-0.80; P<0.0001), prolonged PFS (HR: 0.66,95% CI: 0.55-0.79; P<0.0001) and did not increase overall incidence of treatment-related adverse events (TRAEs) (RR: 1.03, 95% CI: 0.97-1.09; P=0.330) in ES-SCLC patients compared with chemotherapy alone. The subgroup analysis found that patients with negative PD-L1 expression (< 1%) benefited in OS, whereas patients with positive PD-L1 expression (≥1%) had no statistically significant difference in OS. There was a statistically significant difference in PFS between PD-L1-negative (< 1%) and PD-L1-positive (≥1%) patients. The addition of a PD-1 inhibitor or PD-L1 inhibitor to the chemotherapy regimen can improve OS and prolong PFS in patients with ES-SCLC.ConclusionsPD-1/PD-L1 inhibitors combination chemotherapy significantly improves PFS and OS in ES-SCLC patients without increasing the overall incidence of TRAEs.

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Prognostic significance of programmed cell death‐ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta‐analysis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 65 publications

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer

Gene expression profiling of circulating tumor cells captured by MicroCavity Array is superior to enumeration in demonstrating therapy response in patients with newly diagnosed advanced and locally advanced non-small cell lung cancer

PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

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