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免疫格局和子宫内膜癌的TAM密度:对免疫检查点抑制剂疗效的影响

Olivia Le Saux^1,2, Renaud Sabatier^3,4, Isabelle Treilleux^5,4

¹Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, "Cancer Immune Surveillance and Therapeutic Targeting" Team, 28 rue Laennec, Lyon 69008, France.

Therapeutic advances in medical oncology

|August 11, 2025

概括

免疫检查点抑制剂 (ICI) 在子宫内膜癌 (EC) 中显示出可变的疗效. 肌层中CD68+瘤相关巨细胞 (TAMs) 密度较低,预测EC患者对ICI的反应更好.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
癌症研究癌症研究

背景情况:

免疫检查点抑制剂 (ICI) 在子宫内膜癌 (EC) 中有效,但响应因不匹配修复 (MMR) 状态而异.
很大一部分MMR缺乏 (MMRd) 或微卫星不稳定性高 (MSI-H) 瘤患者对ICI单疗具有初级耐药性.

研究的目的:

为了研究MMRd/MSI高和MMR熟练/微卫星稳定 (MMRp/MSS) 之间的瘤免疫微环境的差异,EC.
确定EC中ICI治疗耐药性的基础机制.

主要方法:

用ICI治疗的晚期或复发的EC患者的回顾性分析.
瘤样本的多免疫光染色以量化免疫细胞密度和淋巴体结构.
微卫星状态,淋巴结合体/三级淋巴结合体结构和免疫细胞密度与治疗反应的相关性.

主要成果:

与MMRp/MSS瘤相比,MMRd/MSI-H瘤中淋巴结合物/三级淋巴结构的患病率更高 (81%对17%).
在MMRd/MSI-H瘤中观察到CD8+ T效应细胞与B细胞的接近度增加,这表明免疫细胞的合作.
侧膜中CD68+瘤相关巨细胞 (TAM) 的低密度与ICI响应 (OR=11.67) 和准确预测响应 (AUC=0.75) 有意义地相关.

结论:

在MMRd/MSI-H和MMRp/MSS EC瘤之间存在不同的免疫透模式.
与瘤相关的巨细胞密度是EC中ICI反应的潜在预测生物标志物.

关键词:

这是子宫内膜癌的癌症.免疫检查点抑制剂免疫检查点抑制剂巨细胞是什么?巨细胞是什么?

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