ADAM10 modulates the efficacy of T-cell-mediated therapy in solid tumors

Abstract

T-cell-mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti-cancer immune response, cancer-immunity cycle, T-cell priming, trafficking and T-cell cytotoxic capacity. Thus, reinforcing the anti-cancer immune response is needed to improve the effectiveness of T-cell-mediated therapy. Tumor-associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8⁺ T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti-cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T-cell-mediated therapy. ADAM10 cleaves CD8⁺ T-cell-targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8⁺ T-cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T-cell-mediated therapies.

Keywords: ADAM10; CAR T‐cell therapeutic efficacy; T‐cell‐mediated therapies; immune response; solid tumors.