School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.
Department of Thoracic Surgery, Second Hospital of Shandong University, Jinan, 250012, People's Republic of China.
Purinergic Signal. 2019 Mar;15(1):53-67. doi: 10.1007/s11302-018-9641-4. Epub 2019 Feb 26.
In recent years, immunotherapy has produced many unexpected breakthroughs in oncological therapy; however, it still has many deficiencies. For example, the number of patients who are unresponsive to anti-programmed death-ligand 1 (PD-L1), anti-cytotoxic T-like antigen-4 (CTLA4), and anti-programmed death-1 (PD1) therapies cannot be ignored, and the search for an undiscovered immunosuppressive pathway is imminent. Five decades ago, researchers found that activation of the adenosinergic pathway was negatively correlated with prognosis in many cancers. This review describes the entire process of the adenosinergic pathway in the tumor microenvironment and the mechanism of immunosuppression, which promotes tumor metastasis and drug resistance. Additionally, the review explores factors that regulate this pathway, including signaling factors secreted by the tumor microenvironment and certain anti-tumor drugs. Additionally, the combination of adenosinergic pathway inhibitors with chemotherapy, checkpoint blockade therapy, and immune cell-based therapy is summarized. Finally, certain issues regarding treatment via inhibition of this pathway and the use of targeted nanoparticles to reduce adverse reactions in patients are put forward in this review. Graphical Abstract The inhibitors of adenosinergic pathway loaded nanoparticles enter tumor tissue through EPR effect, and inhibit adenosinergic pathway to enhance or restore the effect of immune checkpoint blockade therapy, chemotherapies and immune cell-based therapy. Note: EPR means enhanced penetration and retention, × means blockade.
近年来，免疫疗法在肿瘤治疗中取得了许多出人意料的突破；然而，它仍然存在许多不足之处。例如，抗程序性死亡配体 1（PD-L1）、抗细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）和抗程序性死亡受体 1（PD1）治疗无反应的患者数量不容忽视，寻找未被发现的免疫抑制途径迫在眉睫。五十年前，研究人员发现，腺苷能途径的激活与许多癌症的预后呈负相关。这篇综述描述了肿瘤微环境中腺苷能途径及其免疫抑制机制的全过程，该机制促进了肿瘤的转移和耐药性。此外，该综述探讨了调节该途径的因素，包括肿瘤微环境分泌的信号因子和某些抗肿瘤药物。此外，还总结了腺苷能途径抑制剂与化疗、检查点阻断治疗和免疫细胞为基础的治疗相结合的情况。最后，本文提出了通过抑制该途径治疗以及使用靶向纳米颗粒减少患者不良反应的一些问题。 图表摘要 载有腺苷能途径抑制剂的纳米颗粒通过 EPR 效应进入肿瘤组织，抑制腺苷能途径，增强或恢复免疫检查点阻断治疗、化疗和免疫细胞为基础的治疗效果。 注：EPR 表示增强渗透和保留，×表示阻断。
