{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:52:38Z","timestamp":1792788758965,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014498","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR 20-PAMR-0011"],"award-info":[{"award-number":["ANR 20-PAMR-0011"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-EURE-0013"],"award-info":[{"award-number":["ANR-17-EURE-0013"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Agence Nationale de la Recherche","award":["ANR-11-LABX-0071"],"award-info":[{"award-number":["ANR-11-LABX-0071"]}],"id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Agence Nationale de la Recherche","award":["ANR-11-IDEX-0005-01"],"award-info":[{"award-number":["ANR-11-IDEX-0005-01"]}],"id":[{"id":"https:\/\/ror.org\/00rbzpz17","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["ARC n\u00b0228308_ARCP"],"award-info":[{"award-number":["ARC n\u00b0228308_ARCP"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["AAP ARC 2020 PJA3"],"award-info":[{"award-number":["AAP ARC 2020 PJA3"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IDEX UP AAP EMERGENCE initiative","award":["IDEX-2021-I-053 (PARA-SET project)"],"award-info":[{"award-number":["IDEX-2021-I-053 (PARA-SET project)"]}]},{"name":"Fondation pour la Recherche M\u00e9dicale","award":["EQU202203014701"],"award-info":[{"award-number":["EQU202203014701"]}],"id":[{"id":"https:\/\/ror.org\/04w6kn183","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CEFIPRA","award":["7103-3 (PARA-REPRESS)"],"award-info":[{"award-number":["7103-3 (PARA-REPRESS)"]}],"id":[{"id":"https:\/\/ror.org\/017aem598","id-type":"ROR","asserted-by":"crossref"}]},{"name":"DIM1HEALTH"},{"name":"Fondation ARC","award":["ARCDOC42025120011089"],"award-info":[{"award-number":["ARCDOC42025120011089"]}]},{"name":"Fonds France Canada pour la Recherche"},{"name":"Research Institute of the Children\u2019s Hospital of Philadelphia","id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Cancer hallmarks are characterized by wide-scale changes in gene expression programs. Pioneering studies showed how viral oncogenes target regulatory pathways, but little is known about tumorigenic mechanisms of non-viral pathogens.\n                    <jats:italic>Theileria annulata<\/jats:italic>\n                    is an intracellular parasite (related to apicomplexa parasites causing malaria) which remarkably transforms bovine leukocytes, hijacking host signaling pathways to induce cancer phenotypes, akin to human leukemias. While some host genes contribute to the proliferative or invasive hallmark phenotypes, there is still limited comprehensive understanding of the impact of\n                    <jats:italic>Theileria<\/jats:italic>\n                    infection on host transcription and transformation. We performed a multi-omics meta-analysis to investigate the effect of\n                    <jats:italic>Theileria<\/jats:italic>\n                    infection on cancer hallmarks in bovine B lymphocytes. Combining transcriptomic, proteomic and epigenomic analysis across multiple datasets, we show that\n                    <jats:italic>Theileria<\/jats:italic>\n                    infection suppresses host immune pathways. Specifically, genes encoding innate and adaptive immune mediators are repressed in\n                    <jats:italic>T. annulata<\/jats:italic>\n                    -infected B cells (and in\n                    <jats:italic>T. parva<\/jats:italic>\n                    infected T cells), including downregulation of genes for Toll-like receptors (TLR), inflammasome components of the guanylate binding protein (GBP) family and major histocompatibility complex class (MHC) II genes. Treatment with distinct theilericidal drugs could partially rescue immune gene expression. Mechanistically, we describe alterations in the host epigenome, including loss of activating histone modifications (e.g., H3K18ac, H3K4me3, H3K27ac) on the promoters of repressed immune genes, and enrichment of silencing marks (H3K27me3) on promoters of the\n                    <jats:italic>BOLA<\/jats:italic>\n                    genes and the gene encoding CIITA, the master transcriptional regulator of MHC class II gene expression. Our results suggest that intracellular\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>annulata<\/jats:italic>\n                    and\n                    <jats:italic>T. parva<\/jats:italic>\n                    parasites could drive an immune evasion cancer hallmark in host lymphocytes by epigenetic silencing of genes for innate and adaptive immunity.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014498","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:50:38Z","timestamp":1787939438000},"page":"e1014498","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic silencing of innate and adaptive immunity genes underlies the immune evasion cancer hallmark in Theileria-infected B-cells"],"prefix":"10.1371","volume":"22","author":[{"given":"Marisol","family":"Giacomini","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristeidis","family":"Panagiotou","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve G.","family":"Odette","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Honfozo","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Berthelet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique","family":"Amo","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Dybas","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Department of Pathology and Laboratory Medicine"]},{"name":"The Children\u2019s Hospital of Philadelphia","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Division of Cancer Pathobiology and Division of Protective Immunity"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Orio-Tejada","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kulej","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Department of Pathology and Laboratory Medicine"]},{"name":"The Children\u2019s Hospital of Philadelphia","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Division of Cancer Pathobiology and Division of Protective Immunity"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Villares","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["St. Louis, Missouri, United States of America"],"department":["Department of Biochemistry and Molecular Biophysics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Hennion","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Weitzman","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Department of Pathology and Laboratory Medicine"]},{"name":"The Children\u2019s Hospital of Philadelphia","place":["Philadelphia, Pennsylvania, United States of America"],"department":["Division of Cancer Pathobiology and Division of Protective Immunity"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-0102","authenticated-orcid":true,"given":"Jonathan B.","family":"Weitzman","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, UMR7126 Epigenetics and Cell Fate","place":["Paris, France"]},{"name":"Institut Universitaire de France (IUF)","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"issue":"1","key":"ppat.1014498.ref001","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"D 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