The T-cell niche tunes immune function through modulation of the cytoskeleton and TCR-antigen forces

Cancer patients who present with obesity tend to have increased tumor burden and decreased T-cell function, yet it remains unclear how obesity compromises T-cell mediated immunity. To address this, we modeled the adipose niche using the secretome of cultured adipocytes and assessed the impact of these factors on T-cell function.

We found that these secretomes altered antigen-specific T-cell receptor triggering and activation. RNA-sequencing analysis identified changes in cytoskeletal regulation and actin polymerization in T-cells exposed to the adipocyte secretome. Molecular force measurements were consistent and showed that T-cells exposed to the adipocyte niche display dampened force transmission to the TCR-antigen complex.