Investigating the Role of A2A Signaling in Caffeine-Induced EL4 T-Cell Lymphoma Growth 2258175

Abstract

Abstract Introduction Adenosine A2A receptor signaling suppresses T-cell activation and promotes tumor immune evasion by dampening anti-tumor responses. Preliminary observations suggested that caffeine enhances EL4 lymphoma cell growth, indicating a receptor-mediated mechanism. This study investigates whether caffeine modulates T-cell lymphoma proliferation through A2A receptor signaling. Methods EL4 lymphoma cells and JURKAT T cells were treated with caffeine and with the selective A2A antagonist ZM241385, individually and in combination. Cell proliferation was measured using standard viability assays. In silico docking with SwissDock was performed to compare caffeine and ZM241385 binding affinities for the A2A receptor. Results Caffeine exposure increased proliferation in both EL4 and JURKAT cells, while ZM241385 alone had minimal effect. Co-treatment partially blocked caffeine-induced proliferation, suggesting involvement of A2A receptor signaling. Docking analysis predicted moderate caffeine binding to A2A, supporting a receptor-mediated interaction. Conclusion Caffeine promotes EL4 and JURKAT T-cell lymphoma proliferation through mechanisms consistent with A2A receptor signaling. These findings highlight the importance of evaluating naturally occurring compounds that can alter tumor immune signaling pathways and potentially influence lymphoma progression. Funding Source n/a Topic Categories Translational and Interventional Immunology (TI)