结直肠癌PD-1/PD-L1阻断治疗的耐药研究现状

Research status of resistance to PD-1/PD-L1 blockade colorectal cancer immunotherapy

PD-1/PD-L1阻断治疗是一种新的肿瘤治疗策略,在过去的十年中,PD-1/PD-L1阻断治疗在很多的恶性肿瘤中应用,取得了一定成功。而对于结直肠癌,只有DNA错配修复蛋白缺失(dMMR)微卫星高度不稳定(MSI-H)患者对PD-1/PD-L1的阻断治疗有积极的反应。原发性和获得性耐药,最终可能导致患者的疾病进展。因此,PD-1/PD-L1阻断治疗的耐药仍是阻碍其进一步应用的重大挑战。为克服阻断治疗的耐药性,人们进行了大量基于耐药机制的研究。在这篇综述里,我们概述了PD-1/PD-L1阻断治疗的现状并对其耐药机制进行探讨。对逆转其耐药的方法进行了讨论和展望,希望对提高PD-1/PD-L1阻断治疗疗效有所裨益。

PD-1/PD-L1 blocking therapy is a new strategy for cancer treatment.In the past decade,PD-1/PD-L1 blocking therapy has been applied in a wide range of malignant tumors and achieved certain success.However,for colorectal cancer,only patients with deficiency mismatch repair(dMMR)and microsatellite instability high(MSI-H)have a positive response to PD-1/PD-L1 blocking therapy.Primary or acquired drug resistance may eventually lead to disease progression.Therefore,the resistance of PD-1/PD-L1 blocking therapy is still a major challenge hindering its further application.In order to overcome the resistance of blocking therapy,a large number of studies based on drug resistance mechanism have been carried out.In this review,we summarize the current status of PD-1/PD-L1 blocking therapy and explore the mechanism of drug resistance.The methods to reverse the drug resistance were prospected,hoping to improve the efficacy of PD-1/PD-L1 blocking therapy.