REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1633315
This article is part of the Research TopicMechanisms and Therapeutic Opportunities of T-Cell Impairment in Cancer Immunity and ImmunotherapyView all 10 articles
Immune microenvironment regulation and clinical immunotherapy strategies of metastatic liver cancer
Provisionally accepted
- School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
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Metastatic liver cancer (MLC) remains a leading cause of cancer-related mortality due to the liver's unique immunotolerant microenvironment and high vascularization. Key mechanisms involve KC-mediated fibronectin deposition, neutrophil extracellular traps (NETs), and MDSC-driven T-cell exhaustion. Clinically, therapeutic strategies targeting the tumor microenvironment (TME) such as CSF1R inhibition, CCR2/CCR5 blockade, and CD40 agonism show promise in preclinical and early-phase trials, especially when combined with immunotherapy. However, challenges remain in overcoming systemic immunosuppression. This review summarizes the dual roles of hepatic immune cells including Kupffer cells (KCs), neutrophils, and myeloidderived suppressor cells (MDSCs) in either suppressing or promoting metastatic colonization. We elucidate how the liver's immunological balance, governed by innate and adaptive responses, shifts toward immunosuppression during metastasis, fostering a pro-tumor niche. This synthesis of immunological insights underscores the potential of TME-modulating therapies to improve outcomes in MLC.
Keywords: Metastatic liver cancer, Tumor Microenvironment, innate immune cells, Adaptive Immunity, Kupffer Cells, Immunotherapy
Received: 22 May 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Liu, Li, Liang, Xu, Li and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Sun, School of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
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