Specifically, treatment of macrophages with an A2A agonist recapitulates the hypoxia-driven polarization towards an M2 phenotype, with upregulation of markers such as the transcription factor IRF4 and the tryptophan-metabolizing enzyme IDO, and enhances the growth-supportive ability of NLCs by increasing synthesis of IL-6, which confers growth advantage to CLL cells. Here, IDO1 is linked to B-cell chronic lymphocytic leukemia.