[Advances in mechanical signal-regulated tumor immunity and its therapeutic development]

The clinical efficacy of tumor immunotherapy is constrained by the immuno-suppressive nature of the tumor microenvironment, within which mechanical signals serve as critical modulators of immune responses. Alterations in tumor tissue mechanics-including matrix stiffening, elevated interstitial pressure, and aberrant fluid shear stress-create physical barriers that impede immune cell infiltration and cytotoxic function. Conversely, immune cells detect and interpret these mechanical cues through mechanosensi-tive pathways involving Piezo1, TRPV4, and YAP/TAZ, which regulate their activation, migration, and effector functions. Small-molecule agents targeting these pathways can precisely modulate key mechanosensitive molecules and emerging mechanical immune checkpoints, thereby bridging mechanical sensing with immune effector reprogramming. Interventions that modify microenvironmental mechanical properties-for instance, through extracellular matrix remodeling or softening-can enhance immune cell infiltration and amplify anti-tumor immunity at the tissue level. Engineered mechano-immunotherapeutic strategies, leveraging biomaterials and biomechanical principles, directly modulate membrane mechanics and mechanotransduction in immune or tumor cells to potentiate immune activity and microenvironmental responsiveness. This review synthesizes current knowledge on the mechanical properties of tumors and their microenvironments, the mechanoregulatory mechanisms operating in immune cells, and recent progress in the development of mechanically targeted therapeutics, with the goal of informing future innovation in immuno-oncology.