Fig. 4

ECM hampers activation and migration of immune cells. ECM constructed immunosuppressive environment demonstrate various mechanisms to induce immune escape in TME. Firstly, increasing density and modification of ECM components strikingly enhance the stiffness, then hamper immune cell migration into tumor islets by composing a physical barrier or directly cell-ECM surface inhibition (via interaction or receptors such as DDRs and LAIR-1). Moreover, tenascin-C immobilizes T cells with immunosuppressive cells and stromal cell, thus immune cells are fixed in the ECM. Finally, OPN stimulates PD-1/PD-L1 expression in immune cells, thus induce immunosuppression