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Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future

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Abstract

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.

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

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This work was supported by The Fundamental Research Funds of Shandong University (No. 2018JC006) and Jiangxi Province Outstanding Young Talents Program (20162BCB23034).

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  1. School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People’s Republic of China

    Yi Huang, Zili Gu, Yang Fan, Guangxi Zhai & Guimei Lin

  2. Department of Thoracic Surgery, Second Hospital of Shandong University, Jinan, 250012, People’s Republic of China

    Xiaogang Zhao & Qifeng Sun

  3. School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China

    Yanbin Shi

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Huang, Y., Gu, Z., Fan, Y. et al. Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future. Purinergic Signalling 15, 53–67 (2019). https://doi.org/10.1007/s11302-018-9641-4

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