结直肠癌新辅助免疫治疗的进展与展望

doi:10.19401/j.cnki.1007-3639.2025.07.003

摘要/Abstract

摘要：

近年来，结直肠癌（colorectal cancer，CRC）新辅助免疫治疗取得了显著进展，特别是在错配修复缺陷/高度微卫星不稳定（mismatch repair deficient/microsatellite instability-high，dMMR/MSI-H）患者中展现出突破性疗效。免疫检查点抑制剂（immune checkpoint inhibitor，ICI）在dMMR/MSI-H患者中实现了高达41%~100%的完全缓解（complete response，CR）率，推动了“豁免手术”和“等待观察”策略的临床应用。然而，占CRC大多数的错配修复完整/微卫星稳定（mismatch repair proficient/microsatellite stable，pMMR/MSS）患者对单药ICI反应有限，需通过联合放疗、化疗或靶向治疗等策略提高疗效，现有研究显示，联合方案可使病理学完全缓解（pathological complete response，pCR）率提升至22%~63%。短程放疗（short-course radiotherapy，SCRT）与免疫治疗的协同效应、双免疫治疗的增效潜力及生物标志物[如POLE/POLD1突变、肿瘤突变负荷（tumor mutational burden，TMB）]的精准筛选成为研究热点。疗效评估方面，肠镜、影像学、循环肿瘤DNA（circulating tumor DNA，ctDNA）和人工智能（artificial inteligence，AI）技术的整合有望优化治疗决策。未来需进一步探索pMMR/MSS患者的免疫增敏策略、“器官保留”的长期安全性及多学科协作下的个体化治疗。新辅助免疫治疗正重塑CRC的治疗格局，为患者带来生存质量的改善。

关键词: 结直肠癌, 免疫治疗, 新辅助治疗, 免疫检查点抑制剂, 生物标志物

Abstract:

In recent years, significant progress has been made in neoadjuvant immunotherapy for colorectal cancer (CRC), particularly demonstrating breakthrough efficacy in mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) subtypes. Immune checkpoint inhibitor (ICI) has achieved complete response (CR) rates as high as 41%-100% in this patient subgroup, driving the clinical adoption of “surgery-sparing” and “watch-and-wait” strategies. However, the majority of CRC patients with mismatch repair proficient/microsatellite stable (pMMR/MSS) tumors show limited response to ICI monotherapy, necessitating combination approaches with radiotherapy, chemotherapy, or targeted therapies to enhance efficacy. Current studies indicate that such combined regimens can elevate pathological complete response (pCR) rates to 22%-63%. Key research focuses include the synergistic effects of short-course radiotherapy (SCRT) combined with immunotherapy, the potential of dual-ICI therapy, and precision patient selection using biomarkers such as POLE/POLD1 mutations and tumor mutational burden (TMB). For treatment response assessment, the integration of colonoscopy, imaging, circulating tumor DNA (ctDNA) and artificial intelligence (AI) holds promise for optimizing clinical decision-making. Future efforts should prioritize immunomodulation strategies for pMMR/MSS patients, long-term safety evaluation of organ preservation approaches, and multidisciplinary collaboration to advance personalized therapy. Neoadjuvant immunotherapy is reshaping the CRC treatment paradigm, offering improved survival and quality of life for patients.

Key words: Colorectal cancer, Immunotherapy, Neoadjuvant therapy, Immune checkpoint inhibitor, Biomarker

中图分类号:

张钰洋, 刘骞. 结直肠癌新辅助免疫治疗的进展与展望[J]. 中国癌症杂志, 2025, 35(7): 642-656.

ZHANG Yuyang, LIU Qian. Advances and future perspectives of neoadjuvant immunotherapy in colorectal cancer[J]. China Oncology, 2025, 35(7): 642-656.

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