结直肠癌新辅助抗PD-1/PD-L1治疗的现状与展望

Neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer:Current status and future prospects

由于程序性细胞死亡1/程序性细胞死亡配体1(programmed cell death 1/programmed cell death ligand 1,PD-1/PD-L1)抑制剂可以增加T细胞对肿瘤组织的浸润,已经证明对缺陷型错配修复/高度微卫星不稳定性结直肠癌(colorectalcancer,CRC)具有良好的疗效.然而,PD-1/PD-L1抑制剂对于熟练型错配修复/非高度微卫星不稳定性CRC的有效性仍然不确定.将免疫疗法加入新辅助治疗可能会改变原发性可切除或某些转移性CRC的治疗策略.

Immunotherapy,particularly programmed cell death 1/programmed cell death ligand 1(PD-1/PD-L1)inhibitors,has made revolutionary progress in the treatment strategies for various types of cancer.Regarding colorectal cancer(CRC),the current clinical application of PD-1/PD-L1 inhibitors is primarily categorized based on mutation patterns,including deficient mismatch repair(dMMR)/high microsatellite instability(MSI-H)and proficient mismatch repair(pMMR)or non-high microsatellite instability(non-MSI-H).PD-1/PD-L1 inhibitors have demonstrated good efficacy against dMMR/MSI-H CRC by increasing T-cell infiltration into tumor tissues.However,the effectiveness of PD-1/PD-L1 inhibitors for pMMR/non-MSI-H CRC remains uncertain.Due to the lower prevalence of dMMR/MSI-H in CRC,recent clinical trials have reported combined applications of PD-1/PD-L1 inhibitors with other anti-tumor treatments such as chemotherapy,radiotherapy,and targeted therapy to achieve better therapeutic outcomes.Neoadjuvant therapy,primarily consisting of chemotherapy and radiotherapy,not only downstages the tumor but also provides benefits from local control,thus improving clinical symptoms and quality of life.Integrating immunotherapy into neoadjuvant therapy may alter the treatment approach for potentially resectable or certain metastatic CRC cases.In this article,we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss its future prospects for the treatment of CRC.