易普利姆玛
无容量
免疫疗法
封锁
免疫检查点
肿瘤科
癌症研究
结直肠癌
医学
病态的
完全响应
黑色素瘤
微卫星不稳定性
新辅助治疗
基因组不稳定性
CD8型
临床研究阶段
免疫系统
质量细胞仪
内科学
临床试验
化疗
癌症
生物标志物
癌
FHIT公司
作者
Pedro Batista Tan,Y.L. Verschoor,José G. van den Berg,Sara Balduzzi,Niels F.M. Kok,Marieke E. Ijsselsteijn,Kat Moore,Adham Jurdi,Antony Tin,Paulien Kaptein,Monique E. van Leerdam,John B.A.G. Haanen,Emile E. Voest,Noel F.C.C. de Miranda,Ton N. Schumacher,Lodewyk F.A. Wessels,Myriam Chalabi
出处
期刊:Nature
[Nature Portfolio]
日期:2025-10-20
卷期号:648 (8094): 726-735
被引量:17
标识
DOI:10.1038/s41586-025-09679-4
摘要
Abstract Immune checkpoint blockade has led to paradigm shifts in the treatment of various tumour types 1–4 , yet limited efficacy has been observed in patients with metastatic mismatch-repair-proficient (pMMR) colorectal cancer 5 . Here we report clinical results and in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (10% or less residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Circulating tumour DNA was positive in 26 of 31 patients at baseline, and clearance was observed in 5 of 6 responders before surgery, whereas 19 of 20 non-responders remained circulating tumour DNA positive. Responses were observed despite a low tumour mutational burden in all tumours, whereas chromosomal genomic instability scores were significantly higher in responders than in non-responders. Furthermore, responding tumours had significantly higher baseline expression of proliferation signatures and TCF1, and imaging mass cytometry revealed a higher percentage of Ki-67 + cancer and Ki-67 + CD8 + T cells in responders than in non-responders. These results provide a comprehensive analysis of response to neoadjuvant immune checkpoint blockade in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.
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