PD-1/PD-L1轴的作用及其在胃肠道肿瘤免疫治疗中的意义

The Effects of The PD-1/PD-L1 Axis and Its Implications for Immunotherapy in Gastrointestinal Tract Cancers

程序性死亡受体1(PD-1)是一种抑制性免疫检查点,与程序性死亡受体配体1(PD-L1)结合,调节免疫反应,维持机体免疫系统平衡。肿瘤细胞通过过表达PD-L1与免疫细胞表面的PD-1结合,抑制免疫细胞的活性与功能,导致癌细胞免疫逃逸和肿瘤进展。胃肠道癌症是全球临床上常见且高死亡率的恶性肿瘤,目前系统治疗方案的效果有限。近年来,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs),如PD-1/PD-L1抑制剂在癌症治疗中越来越重要。免疫疗法已被纳入一些胃肠道恶性肿瘤的治疗方案中,与传统治疗方法不同,它是利用各种手段刺激和增强机体免疫功能,最终达到控制肿瘤细胞的治疗策略。然而,尽管PD-1/PD-L1抑制剂在胃肠道肿瘤治疗中显示出潜力,但单一抑制剂治疗效果有限,这可能是由于肿瘤在抑制剂治疗后仍能通过其他途径逃逸免疫攻击,或者存在其他免疫抑制因子的调节。因此,为了进一步提高治疗效果,组合疗法日益受到重视,它可以同时作用于不同的免疫途径,提高免疫治疗的综合效果。然而,为了实现有效的组合疗法,需要深入研究PD-1/PD-L1轴在胃肠道肿瘤发生和发展中的具体作用机制,这有助于制定最佳的治疗策略,并为合适的患者群体提供个体化的治疗方案。本文将介绍PD-1/PD-L1轴在肿瘤发生中的作用及其机制研究进展,并综述PD-1和PD-L1抑制剂在胃肠道肿瘤中的单一和联合治疗策略。

Programmed death-1(PD-1)is an inhibitory immune checkpoint that binds to programmed deathligand 1(PD-L1)to regulate the immune response and maintain immune system homeostasis of the immune system.Through overexpression of PD-L1,tumor cells bind to PD-1 on the surface of immune cells,inhibiting the activity and function of immune cells,leading to immune escape of cancer cells and tumor progression.Gastrointestinal cancer is a common malignancy with a high mortality rate worldwide,and the effectiveness of current systematic treatment options is limited.In recent years,immune checkpoint inhibitors(ICIs)such as PD-1/PD-L1 inhibitors have attracted much attention in cancer therapy.Immunotherapy has been incorporated into the treatment of some gastrointestinal malignancies.Different from traditional treatment,it uses various means to stimulate and enhance the immune function of the body to achieve the therapeutic purpose of controlling and eliminating tumor cells.However,although PD-1/PD-L1 inhibitors have shown potential in the treatment of gastrointestinal tumors,the efficacy of single inhibitor therapy is limited,which may be due to the ability of tumors to escape immune attack through other pathways after inhibitor treatment,or the presence of other immunosuppressive factors.For example,PD-1 and PD-L1 inhibitors can be combined with other immune checkpoint drugs,molecularly targeted drugs,or chemotherapy drugs to simultaneously act on different immune pathways and improve the comprehensive effect of immunotherapy.However,to achieve an effective combination therapy,we need to delve into the specific mechanisms of action of the PD-1/PD-L1 axis in the development and progression of gastrointestinal tumors,which can help to develop the best treatment strategy and provide individualized treatment options for the appropriate patient population.Therefore,future studies should focus on the regulatory mechanisms of PD-1/PD-L1 axis and evaluate the therapeutic effects of different treatment combinations on gastrointestinal tumors.In this paper,we review the research progress of PD-1/PD-L1 axis in tumorigenicity and its mechanism,and review the single and combined treatment strategies of PD-1 and PD-L1 inhibitors in gastrointestinal tumors.