Extracellular matrix remodeling in the tumor immunity

Abstract

The extracellular matrix (ECM) is a significant constituent of tumors, fulfilling various essential functions such as providing mechanical support, influencing the microenvironment, and serving as a reservoir for signaling molecules. The abundance and degree of cross-linking of ECM components are critical determinants of tissue stiffness. In the process of tumorigenesis, the interaction between ECM and immune cells within the tumor microenvironment (TME) frequently leads to ECM stiffness, thereby disrupting normal mechanotransduction and promoting malignant progression. Therefore, acquiring a thorough comprehension of the dysregulation of ECM within the TME would significantly aid in the identification of potential therapeutic targets for cancer treatment. In this regard, we have compiled a comprehensive summary encompassing the following aspects: (1) the principal components of ECM and their roles in malignant conditions; (2) the intricate interaction between ECM and immune cells within the TME; and (3) the pivotal regulators governing the onco-immune response in ECM.

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment

“…CAFs degrade and remodel the ECM by producing MMPs and activating FAK to limit the infiltration of effector immune cells while increasing the recruitment of inhibitory immune cells (such as Tregs, myeloid-derived suppressor cells (MDSCs), and TAMs), thereby suppressing the initiation of immune responses ( 44 ). Immune cells in the tumor microenvironment also play an important role in the degradation and remodeling of ECM ( 45 ), with tumor-associated macrophages (TAMs) being the most common immune inhibitory cells, secreting factors that suppress immune responses, inhibit T cell activity, and promote tumor growth and metastasis ( 46 ). LOX primarily functions in collagen cross-linking, thereby increasing the stability and mechanical strength of the extracellular matrix ( 47 ).…”