新辅助免疫治疗:dMMR/MSI-H局部进展期结直肠癌患者的“黎明之光”

Neoadjuvant immunotherapy:the"light of dawn"in patients with dMMR/MSI-H locally advanced colorectal cancer

局部进展期结直肠癌(LACRC)患者术后复发转移风险较高。而新辅助治疗一定程度上有助于改善其预后。但错配修复缺陷(dMMR)/高度微卫星不稳定(MSI-H)LACRC对新辅助(放)化疗敏感性仍然较低,突破这一困境亟待解决。免疫治疗的“横空出世”为该类患者带来了希望的曙光。2013年,免疫治疗被《Science》杂志列为十大科学进展之首。2015年,KEYNOTE-016研究确定了dMMR/MSI-H是免疫治疗疗效的分子标志,从此开创了结直肠癌(CRC)领域免疫治疗的新纪元,更是在精准医学时代开启了精准免疫治疗的新征程。而免疫治疗能否用于LACRC的新辅助治疗成为了临床上关注的热点。2020年发表在《Nature Medicine》上的荷兰单臂NICHE研究,展现出了令人震惊的效果,标志着开启了CRC新辅助免疫治疗的大门,为dMMR/MSI-H LACRC患者开辟了新的治疗道路,并有望引领开拓不同癌种新辅助治疗的全新视角。

Patients with locally advanced colorectal cancer(LACRC)have a higher risk of recurrence and metastasis.Neoadjuvant therapy can improve the prognosis to some extent.However,the sensitivity of mismatch repair defect(dMMR)/microsatellite instability-high(MSI-H)LACRC to neoadjuvant chemotherapy(chemoradiotherapy)is still low.The emergence of immunotherapy brings hope to these patients.Immunotherapy was listed as the top ten scientific progress by Science magazine in 2013.Based on the study of KEYNOTE-016 in 2015,it is confirmed that dMMR/MSI-H is a biomarker for the efficacy of immunotherapy,thus ushering in a novel era of immunotherapy in the field of colorectal cancer(CRC),and opening a new journey of precision immunotherapy in the era of precision medicine.Whether immunotherapy can be used as neoadjuvant treatment of LACRC has become a hot topic in clinic.The Dutch single-arm NICHE study published in Nature Medicine in 2020 has demonstrated shocking results,marking the opening of the door of neoadjuvant immunotherapy for CRC,opening up a new treatment path for patients with dMMR/MSI-H LACRC,and is expected to lead the development of a novel perspective of neoadjuvant therapy for different kinds of cancer.