This narrative review examines how the physical stiffness of the tumor environment affects cancer progression in solid tumors. The authors looked at how this stiffness influences various immune cells and cancer cell behaviors without testing a specific drug or intervention.
The analysis indicates that stiff tissue can weaken the function of T-cells and natural killer cells. It also pushes macrophages and dendritic cells toward states that suppress the immune system. Additionally, the review notes that cancer-associated fibroblasts remain active, tumor cells undergo a transition that helps them spread, and immune checkpoint proteins are upregulated.
These changes are linked to higher expression of a protein called YAP1, which is associated with resistance to immunotherapy. The review highlights that current strategies to address this include enzymatic degradation, targeting mechanotransduction pathways, using anti-fibrotic drugs, and developing combination therapies. Because this is a narrative review, it summarizes existing ideas rather than reporting new trial data. Readers should view these findings as potential targets for future research rather than proven treatments available today.