Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.

Authors

Mohsin Maqbool, Anju Surendranath, Sadaf Khursheed Baba, Tooba Jawwad, Imadeldin Elfaki, Rashid Mir, Rakesh Kumar, Shahab Uddin, Mohammad Haris, Muzafar Ahmad Macha, Ammira Al-Shabeeb Akil, Mayank Singh, Sameer Mirza, Ajaz Ahmad Bhat

Published in

Cancer communications (London, England). Volume 46. Pages 0045. Epub Sep 24, 2026.

Abstract

The extracellular matrix (ECM) is a dynamic and functionally active component of the tumor microenvironment that critically regulates immune cell trafficking, activation, and persistence. Rather than serving solely as a structural framework, ECM remodeling through collagen reorganization, proteoglycan-dependent chemokine sequestration, and fibroblast-driven matrix stiffening actively contributes to immune exclusion and evasion in solid tumors. This review integrates emerging mechanistic insights into how ECM composition, architecture, and mechanical properties shape spatial immune exclusion, T cell dysfunction, and immune-checkpoint regulation through mechanotransduction, metabolic reprogramming, and altered cytokine and chemokine signaling. Particular emphasis is placed on the coordinated activities of distinct ECM components and cancer-associated fibroblast subtypes in establishing spatially restricted immunosuppressive niches that limit antitumor immunity and therapeutic responsiveness. ECM-targeted therapeutic strategies are critically evaluated by integrating their mechanistic rationale, preclinical efficacy, clinical trial outcomes, and current stage of translational development. The importance of biomarker-guided patient stratification is also highlighted for identifying tumors most likely to benefit from ECM-directed interventions, particularly in combination with immune-checkpoint blockade and other immunotherapies. Finally, recent advances in spatial transcriptomics, proteomics, matrix imaging, and ECM-derived circulating biomarkers are discussed as tools to refine therapeutic targeting, monitor matrix remodeling, and predict treatment response. By conceptualizing the ECM as an active immunoregulatory network rather than a passive physical barrier, the review provides a mechanistic and translational framework for developing next-generation, ECM-informed cancer immunotherapies.

PMID:
42787254
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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