Ellagic acid-protein nano-complex inhibits tumor growth by reducing the intratumor bacteria and inhibiting histamine production

In recent years, there has been growing interest in understanding the role of bacteria within tumors and their potential as targets for cancer therapy. In this work, we developed an ellagic acid (EA) - endogenous protein (eP) nanocomposite (eP-EA) to target tumors by EPR (enhanced permeability and retention), kill bacteria within tumors to regulate anti-tumor immune responses. The potential mechanism of eP-EA treatment is associated with the reduced abundance and diversity of microorganisms within the tumor, culminating with an altered metabolism within the Tumor microenvironment (TME). Among them, the metabolite histamine that contributes to tumor progression, is significantly reduced in the TME after eP-EA treatment. We show that one possible mechanism by which these microbes promote tumor growth is through the production of histamine. This work suggests that the ellagic acid (EA)-protein nano complex can enhance cancer immunotherapy by targeting the intratumoral bacteria and reduce their production of histamine, delineating the potential relationship between intratumor bacteria and their impact on tumors. Our work suggests that the EA-protein nano complex can enhance cancer immunotherapy by targeting the intratumoral bacteria, suggesting the role of bacterial metabolites in contributing to tumor progression.