Abstract
Microbiome, including bacteria, fungi, and viruses, plays a crucial role in shaping distal and proximal anti-tumor immunity. Mounting evidence showed that commensal microbiome critically modulates immunophenotyping of hepatocellular carcinoma (HCC), a leading cause of cancer-related death. However, their role in anti-tumor surveillance of HCC is still poorly understood. Herein, we spotlighted growing interests in how the microbiome influences the progression and immunotherapeutic responses of HCC via changing local tumor microenvironment (TME) upon translocating to the sites of HCC through different "cell-type niches". Moreover, we summarized not only the associations but also the deep insight into the mechanisms of how the extrinsic microbiomes interplay with hosts to shape immune surveillance and regulate TME and immunotherapeutic responses. Collectively, we provided a rationale for a mechanism-guided fine-tuned microbiome to be neoadjuvant immunotherapy in the near future.