Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed nations, exhibiting significant molecular heterogeneity that impacts prognosis and treatment response, particularly in advanced or recurrent settings. Traditional classification is increasingly supplemented by molecular subtyping (POLE-ultramutated, MSI-high/dMMR, NSMP, p53-mutated/CNH), which provides crucial prognostic information and predicts benefit from immunotherapy. This review summarizes the landscape of predictive biomarkers for immune checkpoint inhibitor (ICI) therapy in EC, emphasizing a new therapeutic scenario for advanced and recurrent EC. Mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), leading to high tumor mutational burden (TMB) and increased neoantigen production, is the most established predictor, resulting in FDA approvals for pembrolizumab and dostarlimab in this subgroup.POLEmutations also confer hypermutation and high immunogenicity, predicting a favorable ICI response. Other biomarkers, including PD-L1 expression and TMB, show variable correlation with response and require further standardization. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs), also influences treatment outcomes. Clinical trials have demonstrated significant survival benefits for ICIs combined with chemotherapy (e.g., dostarlimab/pembrolizumab + carboplatin/paclitaxel) in first-line settings, especially for dMMR/MSI-H EC, and for ICI combinations with targeted agents (e.g., lenvatinib + pembrolizumab) in previously treated patients. Integrating molecular classification and validated biomarkers is essential for optimizing patient selection and developing personalized immunotherapy strategies for EC.
子宫内膜癌（EC）是发达国家最常见的妇科恶性肿瘤，具有显著的分子异质性，这种异质性影响预后和治疗反应，尤其在晚期或复发性病例中。传统的分类方法正日益被分子分型（POLE超突变型、MSI-H/dMMR型、NSMP型、p53突变/CNH型）所补充，该分型提供了关键的预后信息并预测免疫治疗的获益。本综述总结了子宫内膜癌免疫检查点抑制剂（ICI）治疗的预测性生物标志物现状，强调了晚期和复发性EC的新治疗格局。错配修复缺陷（dMMR）或高微卫星不稳定性（MSI-H）导致高肿瘤突变负荷（TMB）和新抗原产生增加，是目前最明确的预测因子，FDA已基于此批准了帕博利珠单抗和多塔利单抗在该亚组中的应用。POLE突变同样导致超突变和高免疫原性，预示着良好的ICI反应。其他生物标志物，包括PD-L1表达和TMB，与治疗反应的相关性不一，需要进一步标准化。肿瘤免疫微环境，包括肿瘤浸润淋巴细胞（TILs），也影响治疗结果。临床试验已证明，在一线治疗中，ICI联合化疗（如多塔利单抗/帕博利珠单抗+卡铂/紫杉醇）尤其在dMMR/MSI-H型EC中，以及在经治患者中ICI联合靶向药物（如仑伐替尼+帕博利珠单抗）能带来显著的生存获益。整合分子分型和经过验证的生物标志物对于优化患者选择和制定个体化的EC免疫治疗策略至关重要。
Predictive Biomarkers for Immunotherapy in Endometrial Carcinoma
肿瘤(癌症)患者之家