Integrated molecular insights into immune regulation and metabolic vulnerabilities in hepatocellular carcinoma

Liver cancer, particularly hepatocellular carcinoma (HCC), presents major clinical challenges due to the multifaceted nature of its tumor immune microenvironment (TIME). The interplay between immune evasion, metabolic reprogramming, and resistance mechanisms creates a complex network that hinders effective treatment. Recent studies have illuminated the roles of transcription factors, such as Zhx2, and immune checkpoint receptors, such as Tim-3, in shaping immunosuppressive phenotypes and disrupting anti-tumor immunity. Additionally, metabolic competition and the influence of microbiota-derived metabolites have been identified as significant contributors to immune cell fate and function. Despite ongoing research, there remain key gaps in understanding how these molecular and metabolic interactions cooperate to maintain an immunosuppressive landscape, with many mechanisms still to be discovered or fully characterized.This Research Topic aims to advance our understanding of the transcriptional and metabolic machinery that orchestrates immune dynamics in the liver cancer TIME. By fostering research at the intersection of molecular regulation and immunometabolism, it seeks to bridge fundamental insights with translational value. The primary objectives are to unravel novel regulatory checkpoints, decipher how local and systemic therapies remodel the TIME, and identify strategies capable of overcoming immune resistance. Researchers are encouraged to employ advanced molecular, cellular, spatial, and computational methodologies that provide mechanistic depth and pave the way for innovative therapeutic interventions.This Research Topic welcomes contributions that highlight both basic research advancements and clinical translation in the context of HCC TIME regulation. The scope encompasses, but is not limited to, the following themes:• Identification and validation of transcription factors, epigenetic regulators, and metabolic enzymes modulating immune cell functions• Dissection of therapy-induced changes in TIME at the transcriptional and metabolic levels, including local and systemic treatment effects• Development and mechanistic evaluation of synergistic therapeutic strategies targeting transcriptional, epigenetic, and metabolic checkpoints• High-resolution mapping of TIME heterogeneity using single-cell and spatial transcriptomics, metabolomics, and integrative computational analyses• Investigation of microbiota-derived metabolites and their effects on immune landscape and immunotherapy response in liver cancer Topic editors: Yong Xu, Siyu Tan, Tixiao Wang, Wenjiang Yan, Xiaojia Song Source: https://www.frontiersin.org/research-topics/79352/integrated-molecular-insights-into-immune-regulation-and-metabolic-vulnerabilities-in-hepatocellular-carcinoma