{"doi":"10.1101/2023.03.03.23286485","title":"A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia","abstract":"Abstract Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2-to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8 + T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.","journal":"medRxiv","year":2023,"id":391254,"datarank":0.3701202575843353,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.05820402633235986,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.05820402633235986,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1024558,"name":"Inge van der Werf","orcid":"0000-0002-8159-399X","position":1,"is_corresponding":false},{"id":438146,"name":"Livius Penter","orcid":"0000-0002-9060-0207","position":2,"is_corresponding":false},{"id":1163569,"name":"Marijn A. Vermeulen","orcid":"0000-0001-8926-1140","position":3,"is_corresponding":false},{"id":1163570,"name":"Farnaz Barneh","orcid":"0000-0003-4715-9732","position":4,"is_corresponding":false},{"id":1163571,"name":"Alicia Perzolli","orcid":"0000-0003-1302-0943","position":5,"is_corresponding":false},{"id":1163572,"name":"Joyce I. Meesters-Ensing","orcid":"0000-0003-0780-9227","position":6,"is_corresponding":false},{"id":310930,"name":"Dennis S. Metselaar","orcid":"0000-0001-5559-2435","position":7,"is_corresponding":false},{"id":1163573,"name":"Thanasis Margaritis","orcid":"0000-0003-4040-2015","position":8,"is_corresponding":false},{"id":314599,"name":"Marta Fiocco","orcid":"0000-0001-5588-0277","position":9,"is_corresponding":false},{"id":314598,"name":"Hester A. de Groot‐Kruseman","orcid":"0000-0001-7038-188X","position":10,"is_corresponding":false},{"id":1163991,"name":"Rubina Moeniralam","orcid":null,"position":11,"is_corresponding":false},{"id":1163574,"name":"Kristina Bang Christensen","orcid":"0000-0002-0008-7359","position":12,"is_corresponding":false},{"id":1163992,"name":"Billie Porter","orcid":null,"position":13,"is_corresponding":false},{"id":38313,"name":"Kathleen L. Pfaff","orcid":"0000-0003-3311-5384","position":14,"is_corresponding":false},{"id":251437,"name":"Jacqueline S. Garcia","orcid":"0000-0003-2118-6302","position":15,"is_corresponding":false},{"id":3736,"name":"Scott J. Rodig","orcid":"0000-0003-1761-9769","position":16,"is_corresponding":false},{"id":3263,"name":"Catherine J. Wu","orcid":"0000-0002-3348-5054","position":17,"is_corresponding":false},{"id":623650,"name":"Henrik Hasle","orcid":"0000-0003-3976-9231","position":18,"is_corresponding":false},{"id":851402,"name":"Stefan Nierkens","orcid":"0000-0003-3406-817X","position":19,"is_corresponding":false},{"id":1163575,"name":"Mirjam E. Belderbos","orcid":"0000-0002-6164-2918","position":20,"is_corresponding":false},{"id":703243,"name":"C. Michel Zwaan","orcid":"0000-0001-6892-8268","position":21,"is_corresponding":false},{"id":1027835,"name":"Olaf Heidenreich","orcid":"0000-0001-5404-6483","position":22,"is_corresponding":false},{"id":1163568,"name":"Joost B. Koedijk","orcid":"0000-0001-6463-3307","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:42.653719Z","pmid":"37961528","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":[]}