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However, the immunobiology of this combination is poorly understood. We performed a comprehensive longitudinal assessment of immunological changes in CML patients treated with nilotinib and interferon\u2010alpha (IFN\u2010\u03b1) within the ALLG CML11 trial (<jats:italic>n<\/jats:italic>\u2009=\u200912) or nilotinib alone (<jats:italic>n<\/jats:italic>\u2009=\u200917). We demonstrate that nilotinib+IFN transiently reduced absolute counts of natural killer (NK) cells, compared with nilotinib alone. Furthermore, CD16<jats:sup>+<\/jats:sup>\u2010cytolytic and CD57<jats:sup>+<\/jats:sup>CD62L<jats:sup>\u2212<\/jats:sup>\u2010mature NK cells were transiently reduced during IFN therapy, without affecting NK\u2010cell function. IFN transiently increased cytotoxic T\u2010lymphocyte (CTL) responses to leukaemia\u2010associated antigens (LAAs) proteinase\u20103, BMI\u20101 and PRAME; and had no effect on regulatory T cells, or myeloid\u2010derived suppressor cells. Patients on nilotinib+IFN who achieved MR4.5 by 12 months had a significantly higher proportion of NK cells expressing NKp46, NKp30 and NKG2D compared with patients not achieving this milestone. This difference was not observed in the nilotinib\u2010alone group. The addition of IFN to nilotinib drives an increase in NK\u2010activating receptors, CTLs responding to LAAs and results in transient immune modulation, which may influence earlier DMR, and its effect on long\u2010term outcomes warrants further investigation.<\/jats:p>","DOI":"10.1111\/bjh.18984","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T07:40:25Z","timestamp":1690011625000},"page":"1127-1136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immune modulation in chronic myeloid leukaemia patients treated with nilotinib and interferon\u2010alpha"],"prefix":"10.1111","volume":"202","author":[{"given":"Yazad D.","family":"Irani","sequence":"first","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Hughes","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-7852","authenticated-orcid":false,"given":"Chung H.","family":"Kok","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jade","family":"Clarson","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7558-9927","authenticated-orcid":false,"given":"David T.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"},{"name":"Department of Haematology Royal Adelaide Hospital  Adelaide South Australia Australia"},{"name":"The Australasian Leukaemia and Lymphoma Group  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"},{"name":"Department of Haematology Royal Adelaide Hospital  Adelaide South Australia Australia"},{"name":"The Australasian Leukaemia and Lymphoma Group  Melbourne Victoria Australia"},{"name":"Department of Genetics and Molecular Pathology Centre for Cancer Biology, SA Pathology  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-7981","authenticated-orcid":false,"given":"Susan","family":"Branford","sequence":"additional","affiliation":[{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"},{"name":"Department of Genetics and Molecular Pathology Centre for Cancer Biology, SA Pathology  Adelaide South Australia Australia"},{"name":"Clinical and Health Sciences University of South Australia  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3730","authenticated-orcid":false,"given":"Timothy P.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Precision Cancer Medicine Theme South Australian Health and Medical Research Institute (SAHMRI)  Adelaide South Australia Australia"},{"name":"The University of Adelaide School of Medicine  Adelaide South Australia Australia"},{"name":"Department of Haematology Royal Adelaide Hospital  Adelaide South Australia Australia"},{"name":"The Australasian Leukaemia and Lymphoma Group  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-1533","authenticated-orcid":false,"given":"Agnes S. 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