Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2022 Sep 2;13:992611. doi: 10.3389/fimmu.2022.992611. eCollection 2022.
Anti-PD-1/PD-L1 therapy has shown significant benefits in the treatment of a variety of malignancies. However, not all cancer patients can benefit from this strategy due to drug resistance. Therefore, there is an urgent need for methods that can effectively improve the efficacy of anti-PD-1/PD-L1 therapy. Combining anti-PD-1/PD-L1 therapy with regorafenib has been demonstrated as an effective method to enhance its therapeutic effect in several clinical studies. In this review, we describe common mechanisms of resistance to anti-PD-1/PD-L1 therapy, including lack of tumor immunogenicity, T cell dysfunction, and abnormal expression of PD-L1. Then, we illustrate the role of regorafenib in modifying the tumor microenvironment (TME) from multiple aspects, which is different from other tyrosine kinase inhibitors. Regorafenib not only has immunomodulatory effects on various immune cells, but can also regulate PD-L1 and MHC-I on tumor cells and promote normalization of abnormal blood vessels. Therefore, studies on the synergetic mechanism of the combination therapy may usher in a new era for cancer treatment and help us identify the most appropriate individuals for more precise treatment.
抗 PD-1/PD-L1 治疗在治疗多种恶性肿瘤方面显示出显著的益处。然而，并非所有癌症患者都能从这种策略中受益，因为存在耐药性。因此，迫切需要能够有效提高抗 PD-1/PD-L1 治疗效果的方法。几项临床研究表明，将抗 PD-1/PD-L1 治疗与regorafenib 联合使用是增强其治疗效果的有效方法。在这篇综述中，我们描述了抗 PD-1/PD-L1 治疗耐药的常见机制，包括肿瘤免疫原性缺乏、T 细胞功能障碍和 PD-L1 异常表达。然后，我们从多个方面说明了 regorafenib 在修饰肿瘤微环境（TME）中的作用，这与其他酪氨酸激酶抑制剂不同。regorafenib 不仅对各种免疫细胞具有免疫调节作用，还可以调节肿瘤细胞上的 PD-L1 和 MHC-I，并促进异常血管的正常化。因此，对联合治疗协同机制的研究可能为癌症治疗带来一个新时代，并帮助我们确定最适合的个体进行更精确的治疗。
