Fig. 4. Overview of cellular mechanisms in immune cells influenced by varying ECM stiffness.

In soft ECM environments, there is enhanced T cell proliferation and guidance of CD8⁺ T cell activation, migration, and infiltration. Conversely, a stiff ECM hinders T cell proliferation and reduces CD8⁺ T cell mobility and cytotoxicity. Low ECM stiffness steers naive CD4⁺ T cells toward Th1 polarization and promotes M1 macrophage polarization from M0, aiding in anticancer immune effects. High ECM stiffness directs immature CD4⁺ T cells to Th2 polarization and M2 macrophage polarization from M0, fostering pro-cancer TME effects.