Insights from Biochemical and Mechanical Cues in Immunoregulation

Checkpoint blockade therapies and mRNA vaccines have emerged as powerful therapeutic modalities for treating cancers and infectious diseases. Despite the progress, significant challenges remain in improving precision, efficacy and safety of therapies. Off-target effects and systemic toxicity have been reported resulting from uncontrolled activation of immune cells. Hence, a major obstacle is to optimize immune responses, for example by selectively activating immune cells within the target tissues while limiting their overactivation.A primary function of immune cells, including T cells and NK cells, is to continuously patrol organs in the body to monitor for signs of infection or cellular abnormality. During immunosurveillance, these cells encounter a wide range of tissue microenvironments with distinct biochemical and biophysical properties. Emerging evidence suggest that immune responses are governed not only by biochemical signals (e.g., cytokines and receptor-ligand interactions) but also by physical cues of the local tissues (e.g., stiffness, shape and surface topography). Studies, including ours, demonstrated that substrate stiffness can modulate key effector functions in both T cells and NK cells. It can impact proliferation and influence their differentiation behaviour. However, how these physical cues converge with biochemical signals to orchestrate immune responses remain poorly understood. We believe elucidating these mechanisms would be key for informing the design of next-generation therapeutics.The Special Issue thus aims to address these knowledge gaps in optimizing immune responses in current therapies. Gaining mechanical insights from how immune cells integrate physical and biochemical information, we can understand their response mechanisms in different tissue microenvironments, for example in tumour tissues and inflammatory sites. This can pave the way for developing next generation therapies with greater precision and reduced risk. We welcome novel ideas and technological advances that explore these challenges.Key areas of interest include, but are not limited to: - Biomimetic or Stimuli-Responsive Systems; - Immune Synapse Dynamics; - Mechanobiology in Immune Cell Functions; - Strategies to Reduce Off-Target Effects; - Approaches to Enhance Immune Cell Activation Topic editors: Dilip Shrestha, Huw Colin-York Source: https://www.frontiersin.org/research-topics/76072/insights-from-biochemical-and-mechanical-cues-in-immunoregulation