树突状细胞和PD-1/PD-L1通路相互作用的研究进展

树突状细胞（dendritic cells，DCs）是最强大的抗原呈递细胞，具有引起抗原特异性反应的能力，并且在调节免疫耐受中起重要作用。基于DCs的癌症免疫治疗已有二十多年的研究，是最重要的抗癌免疫疗法之一，但单一疗法在癌症治疗方面效果有限，需要继续深入研究以提高DCs的抗肿瘤作用，并寻找与其他方法协同治疗的方案。靶向于免疫检查点的单克隆抗体在公认的实体和血液恶性肿瘤的临床试验中均获得了成功，并在2018年获得诺贝尔医学奖。免疫检查点阻断疗法旨在解除肿瘤的免疫抑制以增强免疫系统的抗肿瘤作用，其中针对PD-1/PD-L1免疫检查点的阻断治疗已引起相当多的关注。虽然免疫检查点阻断治疗的效果令人鼓舞，但在尚未满足医疗需求的领域中仍需要进一步研究以提高临床效率。理论上DCs的PD-L1和/或T细胞的PD-1基因沉默或表达下调，可增强DCs启动有效的T细胞抗肿瘤反应。因此，将特异性DCs的抗肿瘤免疫治疗与PD-1/PD-L1信号通路阻断相结合的治疗方法是一个有希望的探索之路。本文主要综述DCs的功能、PD-1/PD-L1通路的抗肿瘤作用、DCs和PD-1/PD-L1信号通路相互作用在目前的研究现状以及前景。

Research progress on the interaction between dendritic cells and PD-1/PD-L1 pathway

Dendritic cells(DCs) are the most powerful antigen-presenting cells,which have the ability to cause antigen-specific responses and play an important role in regulating immune tolerance.DCs-based cancer immunotherapy has been studied for more than 20 years and is one of the most important anti-cancer immunotherapies.However,the effect of monotherapy in cancer treatment is limited.In-depth research is needed to improve the anti-tumor effect of DCs and look for synergistic treatment with other methods.Monoclonal antibodies targeted at immune checkpoints have been successful in clinical trials of recognized solid and hematological malignancies,and won the Nobel Prize in Medicine in 2018.Immune checkpoint blocking therapy aims to relieve the immunosuppression of tumors to enhance the anti-tumor effect of the immune system.Among them,blocking therapy for PD-1/PD-L1 immune checkpoints has attracted considerable attention.Although the effect of immune checkpoint blocking therapy is encouraging,further research is still needed to improve clinical efficiency in areas that have not yet met the medical needs.Theoretically,the silencing or down-regulation of PD-L1 of DCs and/or PD-1 of T cells can enhance DCs to initiate effective T cell anti-tumor response.Therefore,the combination of specific DCs anti-tumor immunotherapy and PD-1/PD-L1 signaling pathway blockade is a promising way to explore.This article will mainly review the current research status and prospects of the function of DCs,the anti-tumor effect of PD-1/PD-L1 pathway,and the interaction between DCs and PD-1/PD-L1 signaling pathway.