Figure 2.

The ECM impedes the activation and migration of immune cells. The construction of an immunosuppressive TME through ECM change exhibits diverse mechanisms that promote immune escape. Primarily, the increased stiffness of ECM subsequently impede the migration of immune cells into tumor islets by establishing a physical barrier or directly inhibit cell-ECM surface interactions (through receptors such as DDRs and LAIR-1). Additionally, the presence of TNC immobilizes T cells alongside immunosuppressive cells and stromal cells, thereby entrapping immune cells within the ECM. Ultimately, OPN elicits the upregulation of PD-1/PD-L1 expression in immune cells, consequently leading to the induction of immunosuppression. ECM, extracellular matrix; TME, tumor micro environment; DDRs, discoidin domain receptors; LAIR-1, immunoglobulin-like receptor 1; TNC, Tenascin-C; OPN, Osteopontin.