Journal of Hepatocellular Carcinoma

Tumor Microenvironment Remodelling and Therapeutic Resistance in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) develops within a complex microenvironment shaped by chronic liver injury, stromal remodelling, and altered immune responses. Interactions among malignant cells, immune cells, fibroblasts, vascular and lymphatic endothelial cells, and the extracellular matrix can influence tumor progression and treatment response. This microenvironment is dynamic: systemic and locoregional therapies may alter its cellular composition and signalling networks, while treatment-induced changes may support immune escape and tumor survival. Understanding these reciprocal interactions is central to investigating primary and acquired therapeutic resistance in HCC.

Despite advances in immunotherapy, antiangiogenic therapy, and molecularly targeted treatment, durable disease control remains challenging for many patients with HCC. A clearer understanding of how microenvironmental remodelling contributes to resistance could help identify actionable vulnerabilities, guide rational combination and sequential strategies, and improve biomarker development. Linking mechanistic findings with longitudinal clinical samples and treatment outcomes is particularly important for distinguishing correlates of resistance from causal drivers. This Article Collection aims to connect basic, translational, and clinical research to clarify how the tumor microenvironment shapes therapeutic resistance and how these processes might be targeted to improve treatment response.

We welcome original research, reviews, clinical trial reports, expert opinions, and commentaries addressing microenvironmental remodelling and therapeutic resistance in HCC. Topics of interest include immune cell dysfunction and suppressive cellular networks; fibroblast activity, extracellular matrix remodelling, and tissue mechanics; angiogenesis, lymphangiogenesis, hypoxia, and metabolic adaptation; tumor-stromal communication and treatment-induced plasticity; and mechanisms of resistance to immune checkpoint inhibitors, targeted agents, and locoregional therapies. We also encourage studies using single-cell or spatial profiling, longitudinal sampling, and functionally validated experimental models to identify resistance biomarkers and evaluate strategies for microenvironmental reprogramming. Submissions should establish a clear connection to HCC biology or treatment and offer mechanistic insight or clinical relevance.

Professor Yang Ke is a hepatobiliary surgeon at the Second Affiliated Hospital of Kunming Medical University in Kunming, China. His research focuses on hepatocellular carcinoma, with particular interests in tumor lymphangiogenesis, tumor microenvironment remodelling, and resistance to immunotherapy. His work integrates clinical investigation with translational research to explore mechanisms of tumor progression and treatment response. He serves on the Editorial Board of the Journal of Hepatocellular Carcinoma and contributes to editorial and peer review activities across oncology and related biomedical fields.

Dr. Zhengtao Liu is an Associate Professor at Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China, and is also affiliated with the Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health. He received his PhD in Surgery from Guangxi Medical University in 2014 and subsequently undertook postdoctoral research at Zhejiang University and at the Science for Life Laboratory, KTH, Sweden. His research integrates multi-omics analysis, systems biology, and experimental approaches to investigate liver disease, hepatocellular carcinoma, and liver transplantation. His work relevant to this Article Collection includes metabolic regulation of hepatocarcinogenesis, molecular characterization of the tumor microenvironment, and research on targeted strategies to prevent tumor recurrence after liver transplantation. He has also served as a guest editor for research collections addressing systems biology and multi-omics approaches to chronic liver disease.

­­All manuscripts submitted to this Article Collection will undergo a full peer-review; the Guest Advisor for this Collection will not be handling the manuscripts (unless they are an Editorial Board member).

Please review the journal scope and author submission instructions prior to submitting a manuscript.

The deadline for submitting manuscripts is 12th July 2027.

Please contact Rebecca Turner at rebecca.turner@tandf.co.uk  with any questions or requests for discount codes relating to this Article Collection.

Please be sure to select the appropriate Article Collection from the drop-down menu in the submission system.