在新辅助化疗 (KSCC1301-A2) 后的直肠癌免疫检查点状态和瘤基因突变概况
Yu Miyashita1,2, Eiji Oki1, Tomohiro Kamori1
1Department of Surgery and Science, Graduate School of Medical Science Kyushu University Fukuoka Japan.
Annals of gastroenterological surgery
|March 8, 2024
概括
新辅助化疗 (NAC) 通过增加免疫检查点分子和瘤透性淋巴细胞,增强不匹配修复性直肠癌 (pMMR) 的瘤免疫微环境. 这表明pMMR直肠癌可能受益于联合免疫疗法和化疗.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 结肠直肠癌研究研究
背景情况:
- 免疫检查点抑制剂 (ICI) 在不匹配修复能力 (pMMR) 的结肠直肠癌 (CRCs) 中表现出有限的疗效,与缺乏MMR的CRC相比.
- 局部晚期直肠癌 (LARC) 是一个重大的临床挑战,pMMR亚型对当前的免疫疗法反应较差.
- 了解瘤微环境对新辅助化疗 (NAC) 的反应对于开发有效的pMMRCRC治疗策略至关重要.
研究的目的:
- 在新辅助化疗 (NAC) 后调查pMMR LARC瘤微环境的变化.
- 评估免疫检查点抑制剂 (ICI) 作为治疗pMMRCRC的治疗剂的潜力.
- 评估NAC后免疫检查点分子 (ICM) 和瘤透淋巴细胞 (TIL) 的变化.
主要方法:
- 一个随机二期试验 (KSCC1301) 的特设分析,涉及49名接受NAC (S-1/oxaliplatin或FU/folinic acid/oxaliplatin) 的LARC患者.
- 为了进行比较,包括了25名没有NAC手术的直肠癌患者的参考队列.
- 免疫组织化学用于评估ICMs (PD-1,PD-L1,CTLA-4,LAG3) 和TILs (CD8,FOXP3);下一代测序 (NGS) 在23名患者中进行.
主要成果:
- 与参考队列相比,在NAC组中观察到PD-1,CTLA-4和LAG3的显著更高的表达 (p < 0.001).
- 在NAC组中,CD8+和FOXP3+T细胞透率显著增加,CD8/FOXP3比率更高 (p < 0.0001).
- 在对NAC的反应中,NGS分析没有发现与TIL或ICM相关的特定基因变异.
结论:
- 新辅助化疗显著改变pMMR直肠癌中的瘤免疫微环境,增强免疫细胞透和检查点分子表达.
- 观察到的变化表明pMMR直肠癌可能对联合免疫疗法和化疗方案变得更敏感.
- 对组合疗法的进一步研究是有必要的,以改善pMMR LARC患者的治疗结果.
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