{"doi":"10.1016/j.celrep.2022.110695","title":"Oncogenic Vav1-Myo1f induces therapeutically targetable macrophage-rich tumor microenvironment in peripheral T cell lymphoma","abstract":"Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) comprises heterogeneous lymphoid malignancies characterized by pleomorphic lymphocytes and variable inflammatory cell-rich tumor microenvironment. Genetic drivers in PTCL-NOS include genomic alterations affecting the VAV1 oncogene; however, their specific role and mechanisms in PTCL-NOS remain incompletely understood. Here we show that expression of Vav1-Myo1f , a recurrent PTCL-associated VAV1 fusion, induces oncogenic transformation of CD4 + T cells. Notably, mouse Vav1-Myo1f lymphomas show T helper type 2 features analogous to high-risk GATA3 + human PTCL. Single-cell transcriptome analysis reveals that Vav1-Myo1f alters T cell differentiation and leads to accumulation of tumor-associated macrophages (TAMs) in the tumor microenvironment, a feature linked with aggressiveness in human PTCL. Importantly, therapeutic targeting of TAMs induces strong anti-lymphoma effects, highlighting the lymphoma cells' dependency on the microenvironment. These results demonstrate an oncogenic role for Vav1-Myo1f in the pathogenesis of PTCL, involving deregulation in T cell polarization, and identify the lymphoma-associated macrophage-tumor microenvironment as a therapeutic target in PTCL.","journal":"Cell Reports","year":2022,"id":245009,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"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":481944,"name":"Ioan Filip","orcid":null,"position":1,"is_corresponding":false},{"id":421610,"name":"Robert Alberó","orcid":"0000-0001-5527-0997","position":2,"is_corresponding":false},{"id":552752,"name":"Juan Ángel Patiño-Galindo","orcid":"0000-0002-6832-7179","position":3,"is_corresponding":false},{"id":706584,"name":"S. Aidan Quinn","orcid":"0000-0002-6557-9186","position":4,"is_corresponding":false},{"id":225923,"name":"Wen-Hsuan W. Lin","orcid":"0000-0002-5414-7900","position":5,"is_corresponding":false},{"id":509977,"name":"Anouchka P. Laurent","orcid":"0000-0001-7726-4723","position":6,"is_corresponding":false},{"id":706587,"name":"Bobby B. Shih","orcid":"0000-0003-0193-8263","position":7,"is_corresponding":false},{"id":879394,"name":"Jessie Brown","orcid":"0000-0003-2396-5393","position":8,"is_corresponding":false},{"id":706586,"name":"Anisha J. Cooke","orcid":"0000-0003-3999-4797","position":9,"is_corresponding":false},{"id":669776,"name":"Adam L. Mackey","orcid":"0000-0003-0064-6373","position":10,"is_corresponding":false},{"id":29299,"name":"Jonah Einson","orcid":"0000-0002-5564-1003","position":11,"is_corresponding":false},{"id":599164,"name":"Sakellarios Zairis","orcid":null,"position":12,"is_corresponding":false},{"id":556957,"name":"Alfredo Rivas‐Delgado","orcid":"0000-0003-0385-3415","position":13,"is_corresponding":false},{"id":879395,"name":"Maria Antonella Laginestra","orcid":"0000-0003-2012-1283","position":14,"is_corresponding":false},{"id":631913,"name":"Stefano Pileri","orcid":"0000-0001-8032-5128","position":15,"is_corresponding":false},{"id":14337,"name":"Elı́as Campo","orcid":"0000-0001-9850-9793","position":16,"is_corresponding":false},{"id":270227,"name":"Govind Bhagat","orcid":"0000-0001-6250-048X","position":17,"is_corresponding":false},{"id":292065,"name":"Adolfo A. Ferrando","orcid":"0000-0002-6212-8574","position":18,"is_corresponding":false},{"id":261872,"name":"Raúl Rabadán","orcid":"0000-0001-7946-9255","position":19,"is_corresponding":false},{"id":554172,"name":"Teresa Palomero","orcid":"0000-0001-9851-3207","position":20,"is_corresponding":false},{"id":554171,"name":"José R. Cortés","orcid":"0000-0002-4457-3850","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:23:34.974895Z","pmid":"35443168","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":[]}