Chen Li, Jiang Xiaoying, Li Yuanheng, Zhang Qiqi, Li Qing, Zhang Xiaoyan, Zhang Meng, Yu Qiongfang, Gao Dian
Department of Pathogen Biology and Immunology, Medical College of Nanchang University, Nanchang 330006, China; Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of Pathogen Biology and Immunology, Medical College of Nanchang University, Nanchang 330006, China.
Clin Immunol. 2022 Apr;237:108962. doi: 10.1016/j.clim.2022.108962. Epub 2022 Feb 25.
Immune checkpoint inhibitors (ICIs), including anti-programmed cell death-1/anti-programmed cell death ligand-1 (anti-PD-1/PD-L1) therapy, have elicited impressive clinical outcomes in several malignancies. This is regarded as a pivotal breakthrough in cancer treatment. However, a vast majority of colorectal cancer (CRC) cases are microsatellite stable (MSS) and respond poorly to anti-PD-1/PD-L1 immunotherapies. Since ICIs serve as rescuers for immune cell-mediated cancer cell elimination, the limited efficacy of anti-PD-1/PD-L1 treatments may be attributed to the privileged tumor microenvironment (TME), which is characterized by unavailable immunosurveillance. Thus, it is essential to modify the pre-existing disordered immune system prior to the application of an anti-PD-1/PD-L1 therapy. In this review, to overcome unsatisfactory immunotherapy in CRC patients with MSS, we discussed various combination therapies based on TME reconstruction for improving the susceptibility to anti-PD-1/PD-L1 treatment.
免疫检查点抑制剂（ICI），包括抗程序性细胞死亡蛋白1/抗程序性细胞死亡配体1（抗PD-1/PD-L1）疗法，已在多种恶性肿瘤中取得了令人瞩目的临床疗效。这被视为癌症治疗的一项关键突破。然而，绝大多数结直肠癌（CRC）病例是微卫星稳定（MSS）的，对抗PD-1/PD-L1免疫疗法反应不佳。由于ICI充当免疫细胞介导的癌细胞清除的拯救者，抗PD-1/PD-L1治疗的有限疗效可能归因于具有特权的肿瘤微环境（TME），其特征是免疫监视无法发挥作用。因此，在应用抗PD-1/PD-L1疗法之前，改变预先存在的紊乱免疫系统至关重要。在本综述中，为了克服MSS型CRC患者免疫治疗效果不佳的问题，我们讨论了基于TME重建的各种联合疗法，以提高对抗PD-1/PD-L1治疗的敏感性。
