Table_1_Myeloid-derived suppressor cells in peripheral blood as predictive biomarkers in patients with solid tumors undergoing immune checkpoint therapy: systematic review and meta-analysis.docx

BackgroundImmunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient responses to these treatments vary significantly. The absence of reliable predictive and prognostic biomarkers hampers the ability to foresee outcomes. This meta-analysis aims to evaluate the predictive significance of circulating myeloid-derived suppressor cells (MDSC) in patients with solid tumors undergoing ICI therapy, focusing on progression-free survival (PFS) and overall survival (OS).
MethodsA comprehensive literature search was performed across PubMed and EMBASE from January 2007 to November 2023, utilizing keywords related to MDSC and ICI. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) directly from the publications or calculated them based on the reported data. A hazard ratio greater than 1 indicated a beneficial effect of low MDSC levels. We assessed heterogeneity and effect size through subgroup analyses.
ResultsOur search yielded 4,023 articles, of which 17 studies involving 1,035 patients were included. The analysis revealed that patients with lower levels of circulating MDSC experienced significantly improved OS (HR=2.13 [95% CI 1.51–2.99]) and PFS (HR=1.87 [95% CI 1.29–2.72]) in response to ICI therapy. Notably, heterogeneity across these outcomes was primarily attributed to differences in polymorphonuclear MDSC (PMN-MDSC) subpopulations and varying cutoff methodologies used in the studies. The monocytic MDSC (M-MDSC) subpopulation emerged as a consistent and significant prognostic marker across various subgroup analyses, including ethnicity, tumor type, ICI target, sample size, and cutoff methodology.
ConclusionsOur findings suggest that standardized assessment of MDSC, particularly M-MDSC, should be integral to ICI therapy strategies. These cells hold the promise of identifying patients at risk of poor response to ICI therapy, enabling tailored treatment approaches. Further research focusing on the standardization of markers and validation of cutoff methods is crucial for integrating MDSC into clinical practice.
Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420095, identifier CRD42023420095.

背景：包括免疫检查点抑制剂（immune checkpoint inhibitor, ICI）疗法在内的免疫治疗策略，其临床潜力日益受到重视。尽管已取得显著进展，但患者对这类治疗的反应差异显著。可靠的预测性与预后生物标志物的缺失，阻碍了治疗结局的预判工作。本荟萃分析旨在评估循环髓系来源抑制细胞（myeloid-derived suppressor cells, MDSC）对接受ICI治疗的实体瘤患者的预测价值，重点关注无进展生存期（progression-free survival, PFS）与总生存期（overall survival, OS）。
方法：我们于2007年1月至2023年11月期间，在PubMed与EMBASE数据库中开展全面文献检索，检索关键词涵盖MDSC与ICI相关主题。我们直接从文献中提取风险比（hazard ratios, HRs）及95%置信区间（confidence intervals, CIs），或根据已报告的数据进行计算。风险比大于1提示低水平MDSC与治疗获益相关。我们通过亚组分析评估异质性与效应量。
结果：本次检索共获取4023篇文献，最终纳入17项研究，涉及1035名患者。分析显示，接受ICI治疗的患者中，循环MDSC水平较低者的OS（HR=2.13 [95% CI 1.51–2.99]）与PFS（HR=1.87 [95% CI 1.29–2.72]）均显著改善。值得注意的是，上述结局的异质性主要源于多形核MDSC（polymorphonuclear MDSC, PMN-MDSC）亚群的差异，以及各研究所采用的截断值方法不同。单核细胞MDSC（monocytic MDSC, M-MDSC）亚群在各类亚组分析中（包括种族、肿瘤类型、ICI靶点、样本量及截断值方法）均表现出稳定且显著的预后标志物价值。
结论：本研究结果表明，对MDSC尤其是M-MDSC进行标准化评估，应成为ICI治疗策略的核心组成部分。这类细胞有望识别出对ICI治疗反应不佳的高风险患者，从而实现个体化治疗方案。未来需聚焦于生物标志物标准化与截断值方法验证的研究，以推动MDSC在临床实践中的应用。
系统评价注册：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420095，标识符为CRD42023420095。