Data Sheet 1_Dual blockade of adenosine A2A and A2B receptors is required to reverse NECA-induced immunosuppression in human macrophages: Implications for cancer immunotherapy.pdf

While current clinical strategies primarily target the A_2A adenosine receptor, emerging evidence suggests that adenosine-mediated immune regulation, particularly in human myeloid cells such as macrophages, involves coordinated signalling through both A_2A and A_2B receptors.

In this study, we define for the first time the adenosine receptor pathways responsible for the immunosuppressive effects of the adenosine analogue 5′-N-Ethylcarboxamidoadenosine (NECA) in human monocyte-derived macrophages and determine the downstream consequences for T cell function. NECA-conditioned macrophages acquired an immunosuppressive, M2-like phenotype, characterised by reduced production of pro-inflammatory cytokines (IL-12, IL-23, IL-6, TNFα) and increased expression of VEGF-A and IL-10.