微卫星不稳定性-作为免疫治疗疗效的泛癌生物标志物的高地位。

IF 4.6 2区医学 Q2 IMMUNOLOGY

Cancer Immunology, Immunotherapy Pub Date : 2025-02-25 DOI:10.1007/s00262-025-03980-x

Thierry Landre, Gaëtan Des Guetz

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引用次数: 0

摘要

背景：微卫星不稳定性高（MSI-H）癌症与免疫检查点抑制剂（ICIs）的特殊益处有关，但对其在各种MSI-H癌症类型中的疗效的研究有限。方法：系统回顾比较晚期MSI-H/dMMR癌症中ICIs与化疗的随机临床试验（rct）。符合条件的研究包括13项随机对照试验，包括1633例结肠直肠癌、胃癌和子宫内膜癌的MSI-H患者。数据分析采用无进展生存期（PFS）和总生存期（OS）的风险比，并按肿瘤类型进行亚组分析。采用Cochrane's Q和I2评估统计异质性。结果：免疫治疗显著改善MSI-H患者的PFS和OS， OS的HR为0.35 (95% CI 0.27-0.46；结论：本荟萃分析确立了MSI-H作为ICIs的预测性生物标志物，支持其在治疗选择中的作用，并强调了以MSI-H/ dmmr为重点的临床试验的必要性。

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Microsatellite instability-high status as a pan-cancer biomarker for immunotherapy efficacy.

Background: Microsatellite instability-high (MSI-H) cancers are linked to exceptional benefit from immune checkpoint inhibitors (ICIs), but studies on their efficacy across various MSI-H cancer types are limited.

Methods: Randomized clinical trials (RCTs) comparing ICIs to chemotherapy in advanced MSI-H/dMMR cancers were systematically reviewed. Eligible studies included 13 RCTs with 1633 MSI-H patients across colorectal, gastric, and endometrial cancers. Data were analyzed using hazard ratios for progression-free survival (PFS) and overall survival (OS), with subgroup analyses by tumor type. Statistical heterogeneity was assessed using Cochrane's Q and I².

Results: Immunotherapy significantly improved PFS and OS in MSI-H patients, with an HR for OS of 0.35 (95% CI 0.27-0.46; p < 0.00001) versus 0.81 for MSS patients. PFS showed a 64% reduced risk of progression (HR = 0.36, 95% CI 0.28-0.46; p < 0.0001). Subgroup analyses highlighted PFS benefits across tumor types: colorectal (HR = 0.28, 95% CI 0.11-0.73), gastric (HR = 0.43, 95% CI 0.27-0.68), and endometrial cancers (HR = 0.34, 95% CI 0.27-0.42).

Conclusions: This meta-analysis establishes MSI-H as a predictive biomarker for ICIs, supporting its role in therapy selection and underscoring the need for MSI-H/dMMR-focused clinical trials.

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来源期刊

Cancer Immunology, Immunotherapy 医学-免疫学

CiteScore

10.50

自引率

1.70%

发文量

207

审稿时长

1 months

期刊介绍： Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.