Tumor immune mechanobiology

Abstract

Tumor microenvironments (TMEs) are not only biochemically complex niches but also mechanically dynamic landscapes that profoundly shape transformed, stromal, and immune cell behavior. This review presents established and emerging insights into the mechanobiology of the stroma and immune cells, particularly cytotoxic T cells, that are extremely promising candidates for anti-tumor immunotherapy. We discuss how complex stromal dynamics and stromal targeting therapies (i.e., antifibrotic, mechanotransduction, and targeting physical properties of the tumor) can enhance immune infiltration and increase susceptibility to immunotherapies. Likewise, mechanical TME features such as stiffness, viscoelasticity, and ECM alignment directly influence T cell infiltration and function through mechanotransduction pathways, including YAP, Rho, and integrin signaling, which can be manipulated to enhance T cell function in solid tumors. We additionally highlight emerging needs to capture spatiotemporal information that are essential for developing design criteria for next-generation “physically optimized” immunotherapies for solid tumor environments.