荷兰癌症研究所Myriam Chalabi课题组研制了错配修复结肠癌的新辅助免疫治疗。这一研究成果发表在2025年10月20日出版的国际学术期刊《自然》上。

在此，该研究组报告来自II期NICHE研究（ClinicalTrials.gov: NCT03026140）的早期pMMR结肠癌患者的临床结果和深入分析。共有31例患者接受了尼武单抗和伊匹单抗的新辅助治疗，随后进行了手术。有效率为26%，包括6例主要病理反应（残余活肿瘤≤10%）的患者。一名临床完全缓解的患者没有接受手术。26/31的患者在基线时循环肿瘤DNA （ctDNA）呈阳性，5/6的应答者在手术前观察到清除，而19/20的无应答者仍然是ctDNA+。尽管所有肿瘤的突变负担都很低，但仍观察到应答，而应答者的染色体基因组不稳定性评分明显高于无应答者。

此外，有反应的肿瘤具有显著更高的增殖特征和TCF1的基线表达，成像细胞计数显示，与无反应相比，应答者中Ki-67⁺癌和Ki-67⁺ CD8⁺ T细胞的百分比更高。这些结果提供了对早期pMMR结肠癌新辅助ICB反应的全面分析，并确定了患者选择的潜在生物标志物。

附：英文原文

研究人员表示，免疫检查点阻断（ICB）已导致多种肿瘤（1-4）治疗的范式转变，但在转移性错配修复精通（pMMR）结直肠癌患者中观察到的疗效有限5。

Title: Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers

Author: Tan, Pedro B., Verschoor, Yara L., van den Berg, Jos G., Balduzzi, Sara, Kok, Niels F. M., Ijsselsteijn, Marieke E., Moore, Kat, Jurdi, Adham, Tin, Antony, Kaptein, Paulien, van Leerdam, Monique E., Haanen, John B. A. G., Voest, Emile E., de Miranda, Noel F. C. C., Schumacher, Ton N., Wessels, Lodewyk F. A., Chalabi, Myriam

Issue&Volume: 2025-10-20

Abstract: Immune checkpoint blockade (ICB) has led to paradigm shifts in the treatment of various tumour types1-4, yet limited efficacy has been observed in patients with metastatic mismatch-repair proficient (pMMR) colorectal cancer5. 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% residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Circulating tumour DNA (ctDNA) was positive in 26/31 patients at baseline, and clearance was observed in 5/6 responders prior to surgery, while 19/20 non-responders remained ctDNA+. Responses were observed despite a low tumour mutational burden in all tumours, while chromosomal genomic instability scores were significantly higher in responders compared to 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 compared to non-responders. These results provide a comprehensive analysis of response to neoadjuvant ICB in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.

DOI: 10.1038/s41586-025-09679-4

Source: https://www.nature.com/articles/s41586-025-09679-4