Unveiling the Intratumor Microbiome in Liver Cancer - Current Insights and Prospective Applications

Sep 23, 2026

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Intratumor microbiome presence in liver cancer, once considered a sterile tumor compartment, has emerged as a newly identified component of the tumor microenvironment. The review summarizes likely origins from the gut, hematogenous spread, adjacent tissues, and co-metastasis, and explains how intratumor microbes shape immune responses, chronic inflammation, and metabolic pathways. The resulting properties support biomarker potential for prognosis and treatment response, while interactions between microbes and host biology may enable microbiome-modulating therapeutic strategies, along with remaining clinical translation challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Intratumor microbiome and gut-liver axis

High-throughput sequencing approaches

Mechanistic pathways: immunity, inflammation, metabolism

Future clinical implications and challenges

pISSN 2287-2728 eISSN 2287-285X Review [https://doi.org/10.3350/cmh.2024.1039](https://doi.org/10.3350/cmh.2024.1039)[ ](https://doi.org/10.3350/cmh.2024.1039)Clinical and Molecular Hepatology 2025;31:685-705 Unveiling the intratumor microbiome in liver cancer: Current insights and prospective applications Xindi Ke1,2,*, Shangze Jiang1,*, Qiaoxin Wei3,*, Minghao Sun1, Hang Sun4 , Mingchang Pang1, Mei Liu3, Lejia Sun5, Huayu Yang1, and Yilei Mao1 1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; 2Department of Head and Neck Surgical Oncology, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; 3Department of Oncology, Beijing You’an Hospital, Capital Medical University, Beijing; 4 Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing; 5Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China The role of the gut microbiome in the development and progression of liver cancer has long been recognized. However, the presence of microbes in tumors that were previously considered sterile has only recently been discovered. The intratumor microbiome in liver cancer likely originates from various sources, including the gut, hematogenous spread from other mucosal locations, adjacent non-cancerous tissues, and co-metastasis with the tumor cells. As a newly discovered component of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, modulates metabolic pathways, and exerts other influences in liver cancer. These unique features offer potential new biomarkers for liver cancer prognosis and treatment response. Exploring the complex interactions between intratumor microbiome and the host to modulate or target the intratumor microbiome may provide new avenues for liver cancer treatment. This article provides a comprehensive review of our current understanding regarding the potential origins of the intratumor microbiome in liver cancer, its unique characteristics, and the underlying mechanisms by which it affects liver cancer. Furthermore, we discuss the promising clinical implications and potential challenges that remain before this knowledge can be fully integrated into clinical practice. (Clin Mol Hepatol 2025;31:685-705) Keywords: Liver cancer; Microbiome; Clinical significance; Biomarkers; Therapeutic effects Corresponding author : Lejia Sun Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China Tel: +86 025-68306026, Fax: +86 025-68306026, E-mail: sunlej[ia361@163.com](ia361@163.com) [https://orcid.org/0000-0002-7161-1103](https://orcid.org/0000-0002-7161-1103) Huayu Yang Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, China Tel: +86 010-69151188, Fax: +86 010-69151188, E-mail: [dolphinyahy@hotmail.com](dolphinyahy@hotmail.com) [https://orcid.org/0000-0001-9791-3559](https://orcid.org/0000-0001-9791-3559) Yilei Mao Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730, China Tel: +86 010-69151188, Fax: +86 010-69151188, E-mail: [pumch-liver@hotmail.com](pumch-liver@hotmail.com) [https://orcid.org/0000-0003-0449-4223](https://orcid.org/0000-0003-0449-4223) *These authors contributed equally. Editor: Terence Kin Wah Lee, The Hong Kong Polytechnic University, Hong Kong Received : Nov. 19, 2024 / Revised : Jan. 8, 2025 / Accepted : Ja

FAQs

What are the proposed origins of the intratumor microbiome in liver cancer?

The intratumor microbiome in liver cancer likely originates from the gut, hematogenous spread from other mucosal sites, adjacent non-cancerous tissues, and co-metastasis with tumor cells.

How does the intratumor microbiome influence liver cancer biology?

As part of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, and modulates metabolic pathways that affect liver cancer progression.

What clinical applications does the review highlight for intratumor microbiome research?

Unique microbial features could serve as biomarkers for liver cancer prognosis and treatment response, and targeting or modulating the intratumor microbiome may offer new therapeutic avenues, pending remaining challenges before clinical integration.

Sep 23, 2026

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