Mechanoimmunology: molecular-scale forces govern immune cell functions

Immune cell recognition of antigens is a pivotal process in initiating immune responses against injury, pathogens, and cancers. Breakthroughs over the past decade support a major role for mechanical forces in immune responses, laying the foundation for the emerging field of mechanoimmunology.

immune receptor signaling is governed by a complex regulatory network involving cross-talk and feedback loops between chemical and physical signals.

With the field of mechanoimmunology still in its infancy, further studies are required to elucidate the exact mechanisms that allow immune receptors to sense and regulate mechanical stimuli.

Potential major advance in cancer treatment ?

In recent years, immunotherapy has emerged as the biggest breakthrough in modern cancer treatment. With the development of chimeric antigen receptors (CARs), we are getting closer to achieving high specificity with reduced risks of off-tumor cytotoxicity, with clinical trials employing CAR T-cells achieving unprecedented remission rates (Frey and Porter, 2016). The role of mechanosensing in antigen discrimination is key to engineering improved CARs that will amplify minute differences in antigen structure to exclusively target tumor antigens. To this end, a deeper understanding of TCR-mediated mechanosensing is required. Key functional insights will no doubt continue to emerge with the design of ever-improving tension probes (Liuet al., 2017) and the development and refinement of novel biophysical tools. Improved in vivo imaging capabilities will likely be crucial, since immune cells move through and operate in such a variety of mechanically distinct 3D microenvironments within organisms. The ability to visualize cells in intact tissues directly will deepen our understanding of the unique mechanobiological mechanisms regulating immune cells and the influence of the mechanical landscape on their migration and functions. This is already becoming a reality, with Eric Betzig’s new adaptive optical-lattice light sheet microscope (AO-LLSM) allowing high-speed, high-resolution in vivo imaging of dynamic subcellular processes in 3D (Liu et al., 2018b). By combining this technology with genetically expressed force sensors, we may soon be able to map molecular-scale mechanical forces in and on cells deep within the complex tissues of living organisms.