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Abstract: NR4A1 is a nuclear receptor that plays a key role in regulating the tumor microenvironment (TME) and interactions between immune and lymphoma cells in aggressive lymphomas. Despite growing insights into its function, how NR4A1 modulates immune responses and influences lymphoma cell growth remains unclear. In this study, we investigate the impact of NR4A1 on immune cells, particularly T cells and macrophages, as well as the cellular and molecular mechanisms contributing to tumor progression. Using advanced single-cell RNA sequencing and functional immune analyses, we analyze NR4A1-mediated signaling pathways in the TME. Our findings may pave the way for novel therapeutic approaches targeting NR4A1 in immune modulation and lymphoma treatment.