Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related mortality globally. The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment landscape for advanced HCC, offering durable responses for a subset of patients. However, both primary and acquired resistance remain significant challenges that limit overall efficacy. The tumor immune microenvironment (TIME) is a critical determinant of ICI response, and its modulation by various concomitant or sequential therapies is a rapidly evolving area of research.
Current HCC management is inherently multimodal. Most patients receiving ICIs have previously been treated with, or are concurrently receiving, other modalities, including locoregional therapies (e.g., TACE, ablation), tyrosine kinase inhibitors (TKIs, such as sorafenib), and, in some cases, antibiotics that affect the gut microbiome. Each of these interventions can profoundly alter the TIME and systemic immunity, potentially synergizing with or antagonizing immunotherapy. This special issue will dissect the multifaceted impact of these common medical treatments on immunotherapy outcomes, exploring mechanistic insights, clinical evidence, and strategies to harness their interactions for improved patient survival.
This Research Topic aims to synthesize current knowledge and stimulate novel research on the complex interactions between conventional liver cancer treatments and the efficacy of immunotherapy. We seek to elucidate the mechanisms—whether immunostimulatory or immunosuppressive—by which locoregional therapies, systemic agents (such as TKIs and VEGF inhibitors), and ancillary treatments (including antibiotics) modulate the tumor immune microenvironment and systemic immunity. A core objective is to move beyond observational data towards mechanistic understanding, providing a foundation for rational treatment sequencing and combination strategies. Ultimately, this collection aims to provide translational insights that can guide clinical decision-making to overcome resistance and improve survival outcomes for patients with hepatocellular carcinoma undergoing immunotherapy.
This Research Topic welcomes the submission of Original Research, Reviews, Systematic Reviews, Mini-Reviews, Perspectives, and Clinical Trials exploring the interplay between established HCC treatments and immunotherapy. Specific themes of interest include, but are not limited to: o The immunomodulatory effects of locoregional therapies (e.g., surgery, TACE, TARE, RFA, SBRT) on the tumor microenvironment and subsequent ICI response. o The impact of tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents (e.g., sorafenib, lenvatinib, bevacizumab) on immune cell function and their synergy with ICIs. o The impact of various immunotherapies on the HBV reactivation in HCC. o The influence of antibiotic use and gut microbiome composition on immunotherapy efficacy in HCC patients. o Clinical studies focusing on novel treatment sequences, combinations, and biomarkers to predict patient response in multimodal therapy settings. o Mechanistic insights from pre-clinical models elucidating how conventional therapies alter the immune landscape of liver cancer.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Community Case Study
Curriculum, Instruction, and Pedagogy
Data Report
Editorial
FAIR² Data
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
