{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:12:33Z","timestamp":1792815153010,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017035","name":"Fondation ISREC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007863","name":"Lunds Tekniska H\u00f6gskola, Lunds universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007863","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016413","name":"Mats Paulssons Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016413","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Acute myeloid leukemia (AML) patients have limited effect from T\u2010cell\u2010based therapies, such as PD\u20101 and CTLA\u20104 blockade. However, recent data indicate that AML patients with <jats:italic>TP53<\/jats:italic> mutation have higher immune infiltration and other immunomodulatory therapies could thus potentially be effective. Here, we performed the transcriptional analysis of distinct T\u2010cell subpopulations from <jats:italic>TP53<\/jats:italic>\u2010mutated AML to identify gene expression signatures suggestive of altered functional properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD8<jats:sup>+<\/jats:sup> cytotoxic T lymphocytes (CTLs), conventional helper T cells (Th), and regulatory T cells (Tregs) were sorted from peripheral blood of AML patients with <jats:italic>TP53<\/jats:italic> mutation (n\u00a0=\u00a05) and healthy donors (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), using FACS, and the different subpopulations were subsequently subjected to RNA\u2010sequencing. Differentially expressed genes were identified and gene set enrichment analysis (GSEA) was performed to outline altered pathways and exhaustion status. Also, expression levels for a set of genes encoding established and emerging immuno\u2010oncological targets were defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed altered transcriptional profiles for each of the T\u2010cell subpopulations from <jats:italic>TP53<\/jats:italic>\u2010mutated AML as compared to control subjects. IFN\u2010\u03b1 and IFN\u2010\u03b3 signaling were stronger in <jats:italic>TP53<\/jats:italic>\u2010mutated AML for both CTLs and Tregs. Furthermore, in <jats:italic>TP53<\/jats:italic>\u2010mutated AML as compared to healthy controls, Tregs showed gene expression signatures suggestive of metabolic adaptation to their environment, whereas CTLs exhibited features of exhaustion\/dysfunction with a stronger expression of <jats:italic>TIM3<\/jats:italic> as well as enrichment of a gene set related to exhaustion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results provide insights on mechanisms underlying the inadequate immune response to leukemic cells in <jats:italic>TP53<\/jats:italic>\u2010mutated AML and open up for further exploration toward novel treatment regimens for these patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4661","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T05:52:35Z","timestamp":1647496355000},"page":"3023-3032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Transcriptional profiling demonstrates altered characteristics of <scp>CD8<\/scp><sup>+<\/sup> cytotoxic T\u2010cells and regulatory T\u2010cells in <i><scp>TP53<\/scp>\u2010<\/i>mutated acute myeloid leukemia"],"prefix":"10.1002","volume":"11","author":[{"given":"Milad","family":"Abolhalaj","sequence":"first","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"CREATE Health Cancer Center, Medicon Village (Building 406) Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Sincic","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"CREATE Health Cancer Center, Medicon Village (Building 406) Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Lilljebj\u00f6rn","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Sand\u00e9n","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7661-0284","authenticated-orcid":false,"given":"Alar","family":"Aab","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"CREATE Health Cancer Center, Medicon Village (Building 406) Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"H\u00e4gerbrand","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ellmark","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl A. K.","family":"Borrebaeck","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"CREATE Health Cancer Center, Medicon Village (Building 406) Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thoas","family":"Fioretos","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine Lund University  Lund Sweden"},{"name":"Department of Clinical Genetics and Pathology University and Regional Laboratories Region Sk\u00e5ne  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1421-8081","authenticated-orcid":false,"given":"Kristina","family":"Lundberg","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Medicon Village (Building 406) Lund University  Lund Sweden"},{"name":"CREATE Health Cancer Center, Medicon Village 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