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国家癌症中心,国家肿瘤临床医学中心研究中心,中国医学科学院北京协和医学院肿瘤医院结直肠外科,北京 100021
Received:04 June 2025,
Revised:2025-07-13,
Published:30 July 2025
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Yuyang ZHANG, Qian LIU. Advances and future perspectives of neoadjuvant immunotherapy in colorectal cancer[J]. China Oncology, 2025, 35(7): 642-656.
Yuyang ZHANG, Qian LIU. Advances and future perspectives of neoadjuvant immunotherapy in colorectal cancer[J]. China Oncology, 2025, 35(7): 642-656. DOI: 10.19401/j.cnki.1007-3639.2025.07.003.
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。
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 s
election 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.
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