Increased extracellular fluid viscosity drives M2-like macrophage polarization to promote breast cancer progression and immunotherapy resistance.

Elevated extracellular fluid viscosity in the tumor microenvironment promotes M2-like macrophage polarization, breast cancer growth, metastasis, and resistance to immunotherapy.

• Why it matters: Understanding physical cues like ECF viscosity is crucial because they may significantly influence tumor progression and therapy resistance, filling a gap in current knowledge focused mainly on biochemical signals.
• What they did: The study used mechanobiological approaches to show that increased ECF viscosity drives macrophages toward a pro-tumoral phenotype via integrin-mediated mechanotransduction involving FAK and STAT3 activation, cytoskeletal remodeling, and nuclear deformation.
• The result: Findings suggest ECF viscosity is a key physical and immunological regulator in breast cancer, highlighting it as a potential biophysical target for therapeutic intervention.