Adenosine (Ado) accumulates in tumor tissues for a long time, which helps to establish an immunosuppressive tumor microenvironment, thereby promoting tumor development. Regulating Ado metabolism is particularly critical for blocking Ado-mediated immunosuppression. Studies have shown that the activity of adenosine kinase (ADK) to catalyze the phosphorylation of Ado has an important regulatory effect on Ado metabolism. Ado accumulated in the tumor microenvironment will occupy the active site of ADK, thereby inhibiting the phosphorylation of Ado. Phosphate can protect ADK from inactivation and restore the activity of ADK. Here, Professor Yuan Quan from Hunan University, Professor Sun Zhijun from Wuhan University Dental Hospital, and Associate Professor Tan Jie from Hunan University designed a calcium phosphate-enhanced iron-based metal organic framework (CaP@Fe-MOFs) to reduce the accumulation of Ado, thereby inhibiting Ado The immunosuppressive response of tumor microenvironment mediated.

CaP@Fe-MOFs can regulate Ado metabolism by promoting ADK-mediated phosphorylation and alleviating hypoxia in the tumor microenvironment. In addition, CaP@Fe-MOFs can also enhance the anti-tumor immune response by regulating Ado, including increasing T lymphocytes and dendritic cells and reducing regulatory T lymphocytes. This article uses CaP@Fe-MOFs to treat mouse tumors and proves that it can effectively alleviate Ado-mediated immunosuppressive response and inhibit tumor growth. This study provides a new general strategy for blocking Ado-mediated immune suppression in the tumor microenvironment and further improving the effect of in vivo immunotherapy.