{"doi":"10.1002/hon.70096_473","title":"473 | LncRNA‐BCYRN1 DRIVES THE POLARIZATION OF TUMOR‐ASSOCIATED MACROPHAGES TOWARDS THE M2 PHENOTYPE IN NK/T CELL LYMPHOMA","abstract":"Background: NK/T-cell lymphoma (NKTCL) is characterized by a complex immune microenvironment, which plays a crucial role in the occurrence, progression, metastasis, and treatment response of the tumor. Long non-coding RNAs (lncRNAs) have been shown to exert significant effects on the regulation of tumor development and drug resistance. However, the role of BCYRN1 in the tumor microenvironment of NKTCL remains unclear. Methods: In this study, we induced THP-1 cells into a macrophage model and modulated BCYRN1 expression via plasmid-mediated knockdown and overexpression. We employed quantitative real-time PCR (qRT-PCR) and flow cytometry to investigate the relationship between BCYRN1 and macrophage polarization. The impact of BCYRN1 on the oxidative phosphorylation (OXPHOS) pathway was assessed using the Seahorse XF assay. Oligomycin was used to selectively inhibit the OXPHOS pathway to elucidate the connection between macrophage polarization and OXPHOS activity. Finally, we utilized a Transwell co-culture system to analyze the effects of BCYRN1-induced M2 macrophages on tumor cell growth and drug resistance. Results: BCYRN1 is overexpressed in NK/T-cell lymphoma cells, and its expression is also elevated in exosomes derived from these cells. Macrophages efficiently take up these exosomes, thereby modulating their functions. An increase in BCYRN1 within macrophages activates the oxidative phosphorylation signaling pathway and promotes the polarization of macrophages towards the M2 phenotype. Inhibition of the OXPHOS pathway significantly attenuates the BCYRN1-mediated M2 polarization of macrophages. Co-culture experiments with macrophages (treated with exosomes from NKTCL cells) and wild-type SNK6 cells reveal that BCYRN1 in NKTCL cell-derived exosomes promotes M2 polarization of macrophages, which in turn enhances tumor cell proliferation and chemoresistance. Conclusions: Our study reveals that BCYRN1 serves as a valuable prognostic biomarker in NK/T-cell lymphoma. BCYRN1 promotes tumor progression, development, and immune evasion by inducing the polarization of tumor-associated macrophages towards the M2 phenotype. Our findings highlight the feasibility of combining oxidative phosphorylation inhibitor with asparaginase therapy for the treatment of NKTCL. Figure 1. Correlation between TAMs and NKTCL. Figure 2. BCYRN1 promotes M2 polarization of tumor cells. Figure 3. BCYRN1 activates the oxidative phosphorylation pathway in macrophages. Figure 4. BCYRN1 promotes M2 polarization of macrophages via the oxidative phosphorylation pathway. Figure 5. BCYRN1 from NKTCL exosomes promotes M2 polarization of macrophages, thereby enhancing tumor growth and drug resistance. Figure 6. Schematic model of BCYRN1 promoting tumor growth in the NKTCL microenvironment. Research funding declaration: This work was supported by grants from the National Natural Science Foundation of China (Nos. 82170181 and 82370188) to Liang Wang Keywords: microenvironment; tumor biology and heterogeneity; aggressive t-cell non-Hodgkin lymphoma No potential sources of conflict of interest.","journal":"Hematological Oncology","year":2025,"id":568516,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1349066,"name":"Jian Guo","orcid":"0000-0002-0314-4080","position":1,"is_corresponding":false},{"id":1472788,"name":"Lili Zeng","orcid":"0000-0002-1959-510X","position":2,"is_corresponding":false},{"id":522081,"name":"Liang Wang","orcid":"0000-0001-5339-7484","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:52.212268Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}