Immune system and extracellular matrix

The 'Immune system and extracellular matrix' (ECM) refers to the complex, bidirectional interaction between immune cells and the structural network of the tissue microenvironment [1, 2]. This axis is not a single molecular target but a functional system where the ECM provides physical support and biochemical cues that regulate immune cell recruitment, activation, and spatial organization [4, 6]. In pathological states such as cancer and chronic fibrosis, the ECM is often remodeled by immune-derived enzymes like matrix metalloproteinases (MMPs) and lysyl oxidase (LOX), creating a dense, stiffened environment that can exclude therapeutic T cells or promote immunosuppression [1, 10]. Conversely, fragments of the ECM, known as matrikines, can act as endogenous ligands for immune receptors, further driving inflammatory responses [13]. Therapeutic strategies targeting this axis focus on normalizing the ECM to improve drug delivery and immune infiltration, or inhibiting specific remodeling enzymes to halt disease progression [5, 8]. As such, the immune-ECM interaction is a critical area of research for enhancing the efficacy of immunotherapies and treating fibrotic disorders [4, 10].

Other names

Immune-ECM crosstalkImmunomatrixImmune system and ECM organization pathwaysImmune-extracellular matrix axis

Modulation of the tissue microenvironment by inhibiting matrix-remodeling enzymes, blocking cell-matrix adhesion receptors, or neutralizing matrix-bound signaling factors to restore immune infiltration and function.