SPP1 and neoplasm: Immune cells contribute to the elevated stiffness of the tumor matrix through two principal mechanisms that facilitate ECM deposition: firstly, via direct secretion of ECM components such as collagen, fibronectin, and osteopontin; and secondly, by indirectly promoting CAF-mediated matrix production through complex cytokine networks, including TGF-β and platelet-derived growth factor-B 31, 51, 55.