Immune remodeling of liver metastases: From molecular mechanisms to therapeutic strategies

Liver metastasis is an intractable clinical challenge due to profound immunosuppression within the liver metastatic niche (LMN), which fundamentally limits immunotherapy efficacy. The unique immune landscape of LMN is shaped by inter-organ, primary tumor-origin, and intra-lesional heterogeneity, driven by multilayered mechanisms including poor immunogenicity, antigen presentation deficiency, antitumor immune cell dysfunction, hyperactive immunosuppressive cells, spatial immune remodeling and host systemic factors. Temporally, LMN evolves from immune surveillance to immune escape. Notably, distinct primary tumors share certain common LMN features, enabling a potential paradigm shift from primary tumor-based classification to LMN-guided subtyping. Precision strategies integrating multi-omics, dynamic biomarkers, and combinatorial interventions hold promise to overcome LMN-driven resistance. This review delineates the spatiotemporal immune remodeling of the LMN, summarizes current therapeutic strategies, and highlights future translational priorities for precision immunotherapy.