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子宫内膜癌免疫治疗进展:MMR 状态与肿瘤微环境的洞见

英文原题:Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment.

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Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment.

PubMed 2024/11/22(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

子宫内膜癌是最常见的妇科恶性肿瘤之一,早期病例通常可有效治疗,但复发或晚期子宫内膜癌(EC)仍难以管理。免疫治疗,特别是免疫检查点抑制剂,已改变肿瘤治疗方式,其用于EC也显示出良好前景。EC免疫治疗效力的关键因素是肿瘤错配修复(MMR)状态:MMR缺陷型肿瘤具有较高肿瘤突变负荷和较高PD-L1表达,因此更易对帕博利珠单抗、度伐利尤单抗和dostarlimab等免疫检查点抑制剂(ICI)应答。

然而,并非所有MMR缺陷(MMRd)肿瘤均对ICI有应答,尤其是免疫浸润不足、具有“冷”肿瘤微环境(TME)的肿瘤。相比之下,部分具有“热”TME的MMR完整肿瘤对ICI反应良好,凸显MMR状态、肿瘤突变负荷(TMB)和TME之间的复杂相互作用。为克服冷肿瘤耐药,研究者正探索CAR-T 细胞和TIL(肿瘤浸润淋巴细胞)等新疗法,以靶向免疫方式增强治疗效力。本综述讨论EC免疫治疗的当前认识,重点阐述MMR状态、TME组成及新兴细胞疗法的预后和治疗意义。

展开英文摘要原文

Endometrial cancer is one of the most common gynecological malignancies, and while early-stage cases are highly treatable, recurrent or advanced EC remains challenging to manage. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionized treatment approaches in oncology, and its application in EC has shown promising results.

Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab.

However, not all mismatch repair-deficient (MMRd) tumors respond to ICIs, particularly those with a "cold" tumor microenvironment (TME) characterized by poor immune infiltration. In contrast, some MMR-proficient tumors with a "hot" TME respond well to ICIs, underscoring the complex interplay between MMR status, tumor mutational burden (TMB), and TME.

To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

论文信息

作者
Albertí-Valls M、Olave S、Olomí A、Macià A、Eritja N
单位
Oncologic Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), University of Lleida (UdL), Av. Rovira Roure 80, 25198 Lleida, Spain.Spain
文献类型
综述
期刊
Cancers2024 Nov 22
原文标识
PubMed 39682106 · DOI 10.3390/cancers16233918