Zhang Jianwei, Cai Jian, Deng Yanhong, Wang Hui
Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
Oncoimmunology. 2019 Sep 19;8(12):e1663108. doi: 10.1080/2162402X.2019.1663108. eCollection 2019.
: PD-1 inhibitors have been approved for the treatment of dMMR patients with metastatic colorectal cancer, but the efficacy of neoadjuvant treatment with PD-1 in dMMR locally advanced rectal cancer (LARC) patients has not yet been defined. : Two patients with LARC received Nivolumab as neoadjuvant treatment in July 2017. Whole-exome sequencing (WES) and multiplex immunofluorescence analysis were performed. : Of the two patients, one achieved pathological complete response after six cycles of nivolumab followed by surgery. The other patient was confirmed to be clinical complete response after six cycles of nivolumab. "Watch and wait" strategy was performed for anal preservation. WES showed high tumor mutation burden. Multiplex immunofluorescence analysis showed immune microenvironment alternation between pretreatment specimen and post-treatment specimen. : Neoadjuvant nivolumab induced complete response in both of the two patients with LARC. Immunotherapy might be an alternative strategy for neoadjuvant treatment for dMMR/MSI rectal cancer.
程序性死亡受体 1（PD-1）抑制剂已被批准用于治疗错配修复缺陷（dMMR）的转移性结直肠癌患者，但 PD-1 在 dMMR 的局部晚期直肠癌（LARC）患者中的新辅助治疗疗效尚未明确。2017 年 7 月，两名 LARC 患者接受纳武单抗作为新辅助治疗。进行了全外显子组测序（WES）和多重免疫荧光分析。两名患者中，一名在接受六个周期的纳武单抗治疗后再行手术，达到了病理完全缓解。另一名患者在接受六个周期的纳武单抗治疗后被确认为临床完全缓解。采用“观察等待”策略以保留肛门。WES 显示肿瘤突变负荷高。多重免疫荧光分析显示治疗前标本与治疗后标本之间的免疫微环境发生了改变。纳武单抗新辅助治疗在两名 LARC 患者中均诱导出完全缓解。免疫治疗可能是 dMMR/微卫星高度不稳定（MSI）直肠癌新辅助治疗的一种替代策略。
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