Prognostic significance of circulating exosomal PD-L1 in various malignant tumors: A systematic review and meta-analysis

Abstract: Although the prognostic significance of exosomal PD–L1 (exoPD–L1) has been previously reported, its value is still controversial. For the first time, we conducted a meta–analysis to systematically evaluate the prognostic value of exoPD–L1 in various types of cancer. The pooled hazard ratio (HR) and 95% confidence interval (CI) in these studies were used to explore the relationship between these indexes and overall survival (OS), recurrence–free survival (RFS), and progression–free survival (PFS). Utilizing the Newcastle‒Ottawa Scale (NOS), the quality of the listed studies was assessed. Heterogeneity was explored by subgroup analyses. Begg's and Egger's tests assessed publication bias. This meta–analysis included 11 trials involving 964 cancer cases. The pooled results indicate that high–level pre–treatment exoPD–L1 in circulation was associated with worse OS (HR = 2.10, 95% CI 1.51–2.91, P < 0.001), RFS (HR = 1.67, 95% CI 1.18–2.37, P < 0.01) and PFS (HR = 3.49, 95% CI 2.60–4.68, P < 0.001) compared to those with low–level pre–treatment exoPD–L1. However, high fold changes in circulating exoPD–L1 after receiving immune checkpoint inhibitors (ICIs) were correlated with significantly superior OS (HR = 0.19, 95% CI 0.10–0.38, P < 0.001) and PFS (HR = 0.35, 95% CI 0.23–0.52, P < 0.001). Through this meta–analysis, we found that pre–treatment with high levels of exoPD–L1 is associated with a poor prognosis. However, a high fold change in circulating exoPD–L1 following immunotherapy was correlated with a superior prognosis. ExoPD–L1 may have important clinical significance for assessing the prognosis of cancer patients. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Scientific Research Plan Project of Tianjin Education Commission [No. 2018KJ034]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors