Cancer Institute, Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, People's Republic of China.
School of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
Clin Exp Med. 2024 Jul 3;24(1):143. doi: 10.1007/s10238-024-01408-x.
Immune checkpoint inhibitors (ICIs) are approved to treat colorectal cancer (CRC) with mismatch-repair gene deficiency, but the response rate remains low. Value of current biomarkers to predict CRC patients' response to ICIs is unclear due to heterogeneous study designs and small sample sizes. Here, we aim to assess and quantify the magnitude of multiple biomarkers for predicting the efficacy of ICIs in CRC patients. We systematically searched MEDLINE, Embase, the Cochrane Library, and Web of Science databases (to June 2023) for clinical studies examining biomarkers for efficacy of ICIs in CRC patients. Random-effect models were performed for meta-analysis. We pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for biomarkers predicting response rate and survival. 36 studies with 1867 patients were included in systematic review. We found that a lower pre-treatment blood neutrophil-to-lymphocyte ratio (n=4, HR 0.37, 95%CI 0.21-0.67) predicts good prognosis, higher tumor mutation burden (n=10, OR 4.83, 95%CI 2.16-10.78) predicts response to ICIs, and liver metastasis (n=16, OR 0.32, 95%CI 0.16-0.63) indicates resistance to ICIs, especially when combined with VEGFR inhibitors. But the predictive value of tumor PD-L1 expression (n=9, OR 1.01, 95%CI 0.48-2.14) was insignificant in CRC. Blood neutrophil-to-lymphocyte ratio, tumor mutation burden, and liver metastasis, but not tumor PD-L1 expression, function as significant biomarkers to predict efficacy of ICIs in CRC patients. These findings help stratify CRC patients suitable for ICI treatments, improving efficacy of immunotherapy through precise patient management. (PROSPERO, CRD42022346716).
免疫检查点抑制剂 (ICIs) 已被批准用于治疗错配修复基因缺陷的结直肠癌 (CRC)，但反应率仍然较低。由于研究设计和样本量小的异质性，当前预测 CRC 患者对 ICI 反应的生物标志物的价值尚不清楚。在这里，我们旨在评估和量化多种生物标志物预测 CRC 患者对 ICI 疗效的重要性。我们系统地检索了 MEDLINE、Embase、Cochrane 图书馆和 Web of Science 数据库（截至 2023 年 6 月），以寻找评估 CRC 患者中 ICI 疗效的生物标志物的临床研究。对meta 分析采用随机效应模型。我们汇总了预测反应率和生存率的生物标志物的优势比 (OR) 和风险比 (HR) 及其 95%置信区间 (CI)。系统综述共纳入 36 项研究，共 1867 例患者。我们发现，较低的治疗前血液中性粒细胞与淋巴细胞比值（n=4，HR 0.37，95%CI 0.21-0.67）预测预后良好，较高的肿瘤突变负担（n=10，OR 4.83，95%CI 2.16-10.78）预测对 ICI 的反应，肝转移（n=16，OR 0.32，95%CI 0.16-0.63）表明对 ICI 的耐药性，尤其是与 VEGFR 抑制剂联合使用时。但是，CRC 中肿瘤 PD-L1 表达（n=9，OR 1.01，95%CI 0.48-2.14）的预测价值不显著。血液中性粒细胞与淋巴细胞比值、肿瘤突变负担和肝转移，但不是肿瘤 PD-L1 表达，是预测 CRC 患者 ICI 疗效的重要生物标志物。这些发现有助于对适合 ICI 治疗的 CRC 患者进行分层，通过精确的患者管理提高免疫治疗的疗效。（PROSPERO，CRD42022346716）。
