2026-10-13T18:51:04Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33717928 2026-09-14T04:33:14Z category_696 portal_316 item_type_3 month_year_09_2026

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 Foteini Patera (24867844) Meryem Gultekin (24867847) Anna Malecka (24867850) Bryony Heath (24867853) Tajkia Musarrat (24867856) Aanchal Preet Kaur (15160099) Poulam M. Patel (5785028) Stephen J. Hill (481670) Andrew M. Jackson (15458333) Hester A. Franks (24867859) Genetic Immunology adenosine cancer immunotherapy human macrophage NECA receptor <p>Adenosine accumulation within the tumour microenvironment is a major barrier to effective cancer immunotherapy, driving potent immunosuppression through adenosine receptor signalling. 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. Functionally, these macrophages impaired T cell effector responses, markedly reducing Th1-type responses as indicated by ablation of IFNγ production. Importantly, reversal of macrophage polarisation and restoration of T cell function could be achieved by simultaneous blockade of both A_2A and A_2B receptors. These findings identify the potential of simultaneously inhibiting the A_2A and A_2B receptors as a novel key strategy for overcoming adenosine-driven immunosuppression and enhancing the efficacy of cancer immunotherapies targeting the tumour microenvironment.</p> 2026-09-14T04:33:14Z Dataset Dataset 10.3389/fimmu.2026.1845291.s001 https://figshare.com/articles/dataset/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/33717928 CC BY 4.0