Journal Article Review Epublish
PubMed: 42787254 DOI: 10.34133/cancomm.0045
Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.
Cancer Commun (Lond) 46:0045
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
Affiliations
- Department of Cancer Biology and Pharmacology, Thomas Jefferson University, Philadelphia, PA, USA.
- Metabolic and Mendelian Disorders Clinical Research Program, Precision Omics Research and Translational Science, Sidra Medicine, Doha, Qatar.
- Department of Chemistry, College of Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
- Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.
- Department of Medical Laboratory Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
- School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu and Kashmir, India.
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
- Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology, Pulwama, Jammu and Kashmir, India.
- Department of Medical Oncology, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, India.
- Zayed Bin Sultan Centre for Health Sciences, United Arab Emirates University, Abu Dhabi, UAE.
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.
MeSH
Cells, Chemokines, Neoplasms, Biomarkers, Immunotherapy, Fibroblasts, Therapeutics, Extracellular Matrix, Immune Evasion