肿瘤免疫检查点疗法耐药机制的研究进展

Research progress on resistance to tumor immune checkpoint blockade

随着肿瘤免疫学、细胞生物学和分子生物学技术等研究的不断深入,肿瘤免疫治疗在基础研究和临床应用中蓬勃发展,已经成为多种恶性肿瘤的重要治疗手段。肿瘤免疫治疗是通过主动或被动的方法使机体产生肿瘤特异性免疫应答来发挥其抑制和杀伤肿瘤功能的治疗方法,目前主要的免疫治疗方法包括免疫检查点抑制剂、过继性细胞疗法、肿瘤特异性疫苗和小分子免疫药物等。其中,以PD-1/PD-L1抗体为代表的免疫检查点抑制剂通过抑制肿瘤细胞免疫检查点活性,释放免疫刹车,激活杀伤T细胞对肿瘤的免疫应答效应,从而达到抗肿瘤的作用。相较于传统的疗法,其优势在于其抗肿瘤的广谱性和持久性。尽管免疫检查点抑制疗法在治疗癌症方面取得了前所未有的发展,但与治疗肿瘤的其他药物一样,由于肿瘤内在遗传因素及外在环境因素影响,肿瘤的免疫检查点抑制药物也会产生原发或获得性耐药。本文聚焦近年来免疫检查点疗法耐药机制的研究进展,对肿瘤免疫检查点抑制药物的耐药机制进行归纳总结,以促进人们对肿瘤免疫治疗理论和技术的进一步理解。

As research progressed in the fields of tumor immunology,cell biology and molecular biology,tumor immunotherapy have evolved fast in both basic research and clinical application,which has become a major way for cancer treatments.Tumor immunotherapy is the method that can promote tumor-specific immune responses in the human body,either actively or passively,enabling the suppression of tumors.Immune checkpoint block inhibitors,adoptive cell therapy,tumor-specific vaccines,and small-molecule immune drugs are currently the most common types of tumor immunotherapy methods.Immune checkpoint block inhibitors such as PD-1/PD-L1 antibodies can inactivate tumor cell checkpoint,unleash the anti-tumor immune responses of cytotoxic T cells.The biggest advantage of immunotherapy over traditional therapies is the durability and broad spectrum anticancer capability.Despite that tumor immunotherapy has been applied unprecedentedly for the treatment of various cancer,tumor immunotherapy drugs,like other cancer drugs,are inevitably become resistant in tumor due to intrinsic genetic and extrinsic environmental factors.Here we focus on recent progresses of the drug resistance mechanisms in immune checkpoint therapy,promoting our understanding of the immunotherapy theory and technique to overcome the drug resistance of checkpoint block inhibitors.