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Review
. 2019 Mar;15(1):53-67.
doi: 10.1007/s11302-018-9641-4. Epub 2019 Feb 26.

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

Yi Huang  1 , Zili Gu  1 , Yang Fan  1 , Guangxi Zhai  1 , Xiaogang Zhao  2 , Qifeng Sun  2 , Yanbin Shi  3 , Guimei Lin  4
Affiliations
Review

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

Yi Huang et al. Purinergic Signal. 2019 Mar.

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. 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.

Keywords: Adenosine; Immunosuppression; Poor prognosis; Targeted nanoparticles.

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Conflict of interest statement

Conflict of interest

Yi Huang declares that he/she has no competing interest.

Zili Gu declares that he/she has no competing interest.

Yang Fan declares that he/she has no competing interest.

Guangxi Zhai declares that he/she has no competing interest.

Xiaogang Zhao declares that he/she has no competing interest.

Qifeng Sun declares that he/she has no competing interest.

Yanbin Shi declares that he/she has no competing interest.

Guimei Lin declares that he/she has no competing interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Figures

Graphical Abstract
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
Fig. 1
Fig. 1
The entire process of the adenosinergic pathway in the tumor microenvironment and the mechanism of immunosuppression, metastasis and drugs resistance. Note: Positive sign (+) means increasing, Negative sign (-) means decreasing
See this image and copyright information in PMC

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