{"doi":"10.1002/ijc.34405","title":"Dysfunctions of innate and adaptive immune tumor microenvironment in Waldenström macroglobulinemia","abstract":"Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by malignant lymphoplasmacytic cells in the bone marrow (BM). To dissect the pathophysiology of WM, we evaluated clonal cells by mapping of B cell lymphomagenesis with adaptive and innate immune tumor microenvironment (TME) in the BM of WM patients using mass cytometry (CyTOF). In-depth immunophenotypic profiling of WM cells exhibited profound expansion of clonal cells in both unswitched and switched memory B cells and also plasma cells with aberrant expression variations. WM B lymphomagenesis was associated with reduction of most B cell precursors assessed with the same clonally restricted light chain and phenotypic changes. The immune TME was infiltrated by mature monocytes, neutrophils and adaptive T cells, preferentially subsets of effector T helper, effector CTL and effector memory CTL cells that were associated with superior overall survival (OS), in contrast to progenitors of T cells and myeloid/monocytic lineage subsets that were suppressed in WM cohort. Moreover, decrease in immature B and NKT cells was related to worse OS in WM patients. Innate and adaptive immune subsets of WM TME were modulated by immune checkpoints, including PD-1/PD-L1&PD-L2, TIGIT/PVR, CD137/CD137-L, CTLA-4, BTLA and KIR expression. The response of ibrutinib treatment to the reduction of clonal memory B cell was associated with high levels of immature B cells and effector memory CTL cells. Our study demonstrates that CyTOF technology is a powerful approach for characterizing the pathophysiology of WM at various stages, predicting patient risk and monitoring the effectiveness of treatment strategies.","journal":"International Journal of Cancer","year":2022,"id":276204,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":946327,"name":"Gábor Beke","orcid":"0000-0002-3385-1317","position":1,"is_corresponding":false},{"id":356236,"name":"Zachary R. Hunter","orcid":"0000-0002-1689-1691","position":2,"is_corresponding":false},{"id":289951,"name":"Teru Hideshima","orcid":"0000-0003-2939-6224","position":3,"is_corresponding":false},{"id":946784,"name":"Ludmila M. Flores","orcid":null,"position":4,"is_corresponding":false},{"id":946785,"name":"Tatiana Zeleznikova","orcid":null,"position":5,"is_corresponding":false},{"id":946786,"name":"Denisa Harrachova","orcid":null,"position":6,"is_corresponding":false},{"id":946787,"name":"Lubos Klucar","orcid":null,"position":7,"is_corresponding":false},{"id":946328,"name":"Merav Leiba","orcid":"0000-0002-3410-8496","position":8,"is_corresponding":false},{"id":885915,"name":"Ľuboš Drgoňa","orcid":"0000-0002-5089-3201","position":9,"is_corresponding":false},{"id":232462,"name":"Steven P. Treon","orcid":"0000-0001-6393-6154","position":10,"is_corresponding":false},{"id":296306,"name":"Efstathios Kastritis","orcid":"0000-0001-8191-5832","position":11,"is_corresponding":false},{"id":946329,"name":"David M. Dorfman","orcid":"0000-0002-6244-8535","position":12,"is_corresponding":false},{"id":7894,"name":"Kenneth C. Anderson","orcid":"0000-0002-6418-0886","position":13,"is_corresponding":false},{"id":946330,"name":"Jana Jakubı́ková","orcid":"0000-0003-2593-569X","position":14,"is_corresponding":false},{"id":946326,"name":"Dana Cholujová","orcid":"0000-0003-4024-7713","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T00:28:26.545826Z","pmid":"36533670","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":[]}