Single-cell analysis of innate immune cell mechanics: an application to cancer immunology

The innate immune system forms a crucial defense mechanism of the human body against infections and foreign objects, orchestrates wound healing, and restores tissue homeostasis after resolving the insult. Furthermore, innate immune cells launch adaptive immune responses against tumors and mediate phagocytosis of cancer cells and cytotoxic tumor killing. They may also be exploited by cancer cells to promote angiogenesis and metastasis. Although the life cycle and function of innate immune cells require a continuous remodeling of their mechanical properties, data on the biomechanics of different innate immune cell subtypes are scarce. Recent advances in single-cell force spectroscopy have facilitated the exploration of immune cell mechanics at phyiological temperature, aiding in filling this knowledge gap. In this article, we discuss the existing data on the mechanical properties of innate immune cells and provide the first single-cell mechanical characterization of tumor-associated macrophages. The presented data on tumor-associated macrophages showcase the new technical possibilities for decoding immune cell mechanics in cancer, further contributing to our understanding of innate immune cell behavior in disease contexts. Alterations in the tumor microenvironment not only modulate cancer cell progression and invasiveness but also affect the viscoelastic properties of immune cells therein.