MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1672601
This article is part of the Research TopicBreaking Barriers: New Frontiers in Immunotherapy for Resistant CancersView all 5 articles
Targeting Tumor Microenvironmental Barriers to Enhance Immunogenic Cell Death in Solid Tumors
Provisionally accepted
- Zibo Central Hospital, Zibo, China
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Immunogenic cell death (ICD) effectively triggers adaptive immune responses against cancer, yet its clinical application in solid tumors is hindered by tumor microenvironment (TME) barriers. These include immunosuppressive cell populations, dense extracellular matrix, abnormal vasculature, hypoxia, and metabolic suppression, which collectively impede immune infiltration and function. This review evaluates current therapeutic strategies to overcome these barriers, including vascular normalization (restoring abnormal tumor blood vessels to a more structured and functional state to improve perfusion and immune cell infiltration), extracellular matrix (ECM) modulation, alleviation of hypoxia, metabolic reprogramming, immunosuppressive cell targeting, physical remodeling, and nanoparticle-based drug delivery. Clinical evidence highlights the potential of these integrated approaches to enhance ICD-induced antitumor immunity, suggesting promising avenues for improving patient outcomes through combined modulation of the TME and ICD induction.
Keywords: Immunogenic cell death (ICD), Tumor microenvironment (TME), immune suppression, Tumor Microenvironmental Barriers, metabolic reprogramming
Received: 24 Jul 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Long, Zhang and Yi. 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: Mei Long, Zibo Central Hospital, Zibo, China
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