Mechanoimmunology in the solid tumor microenvironment

Abstract

The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology — the interplay between mechanical forces and immune cell behavior — is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.