Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy

Abstract

The extracellular matrix (ECM), closely linked to the dynamic changes in the tumor microenvironment (TME), plays a critical role in modulating tumor immunity. The dual role of the ECM in tumor progression, encompassing both promotion and inhibition, is attributed to its components influencing immune cell activation, migration, and infiltration. This mechanism is intricately connected with the efficacy of immunotherapies. Currently, there is limited understanding of how ECM remodeling spatially and temporally coordinates with immune checkpoint inhibitors (ICIs) or adoptive cell therapies. Furthermore, strategies to selectively target pathological ECM components while preserving their homeostatic functions urgently require systematic investigation. In this review, we summarize current findings on the interplay between ECM and tumor immune regulation, with a particular focus on how key ECM components contribute to immune modulation. Furthermore, we discuss emerging strategies targeting ECM-related mechanisms to enhance the efficacy of immunotherapies, including approaches that remodel the ECM to improve immune infiltration and strategies that synergize with existing immunotherapies. By integrating these insights, we provide a perspective on leveraging ECM-targeted interventions to overcome immune evasion and optimize cancer immunotherapy outcomes.