Cordycepin enhances the Anticancer efficacy of PD-L1 blockade by modulating the tumor microenvironment of colon cancer

Background: PD-L1 blockade has been found to be effective in treating multiple malignancies. Combined therapy is proposed to provide better therapeutic effects. Cordycepin, a prominent bioactive compound found in cordyceps, can inhibit the development of various cancers. Purpose: This study aimed to determine the efficacy of combined anti-PD-L1 antibody and cordycepin in tumor treatment. Methods: A single-cell RNA sequencing was used to analyze the mechanism of combined treatment. Results: Combination therapy of anti-PD-L1 and cordycepin significantly inhibited tumor growth by regulating the T cell ratio and improving the function of CD8⁺T cells. Furthermore, cordycepin promoted the reprogramming of type-II macrophages into type-I macrophages, a process confirmed through flow cytometry analysis of the underlying mechanism. Conclusion: Our findings demonstrate that the combination of anti-PD-L1 and cordycepin effectively suppressed tumor growth by regulating the proportion of T cells and reprograming type-II macrophages.