As for A2AR, genetic deletion of A2BR reduces tumor growth rate (399, 423) while A2BR−/− tumor cells display reduced metastatic potential (359, 367). Notably, administration of A2BR antagonists in tumor-bearing mice reduces tumor growth (315, 398, 399) and metastasis (292, 359, 368) eventually prolonging their survival (359). Mechanistically, antagonism of A2BR in vivo augments the intra-tumoral presence of CD8+ T cells (315, 398), NKT (315, 398) as well as the mRNA levels of IFNγ and CXCL10 (399) and the concentration of TNFα, IFNγ, and GzB (398) in the TME. This intervention further results in decreased accumulation of MDSCc (315, 398) and IL-10 (398), as well as reduced levels of VEGF and angiogenesis (315). Based on encouraging preclinical results, Palobiofarma recently launched a dose escalation Phase I study (NCT03274479) administering PBF-1129, a selective A2BR inhibitor, in patients with advanced Non-Small Cell Lung Cancer (NSCLC).