Intratumoral microbial heterogeneity in HCC reveals a potential therapeutic target

Background & Aims: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its therapeutic challenges are largely influenced by the complexity of the tumor microenvironment (TME). This study aimed to characterize intratumoral microbial heterogeneity, explore its role within the TME, and identify potential antitumor mechanisms and novel microbial targets. Methods: . Results: sp. reshapes the tumor immune microenvironment, particularly influencing immune cell infiltration and metabolic status. Conclusions: sp. exerts potential antitumor effects by regulating glycerophospholipid metabolism and modulating immune cell infiltration. These findings highlight a novel microbial target for HCC treatment. Impact and implications: sp. modulates the tumor microenvironment by regulating glycerophospholipid metabolism and immune cell infiltration. These results are significant for cancer microbiome researchers, oncologists, and translational scientists, highlighting microbial heterogeneity as a previously underrecognized factor in HCC biology. Clinically, the study lays the groundwork for the development of microbiota-based therapeutic strategies or biomarkers, though further mechanistic and translational studies are warranted to evaluate feasibility and safety in human settings.