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Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation

A deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR pat...

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Autores principales: Puzzolo, Maria Cristina, Breccia, Massimo, Mariglia, Paola, Colafigli, Gioia, Pepe, Sara, Scalzulli, Emilia, Mariggiò, Elena, Latagliata, Roberto, Guarini, Anna, Foà, Robin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570842/
https://www.ncbi.nlm.nih.gov/pubmed/36233461
http://dx.doi.org/10.3390/jcm11195594
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author Puzzolo, Maria Cristina
Breccia, Massimo
Mariglia, Paola
Colafigli, Gioia
Pepe, Sara
Scalzulli, Emilia
Mariggiò, Elena
Latagliata, Roberto
Guarini, Anna
Foà, Robin
author_facet Puzzolo, Maria Cristina
Breccia, Massimo
Mariglia, Paola
Colafigli, Gioia
Pepe, Sara
Scalzulli, Emilia
Mariggiò, Elena
Latagliata, Roberto
Guarini, Anna
Foà, Robin
author_sort Puzzolo, Maria Cristina
collection PubMed
description A deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR patients who had received TKI treatment only (TKI-only) or had been previously treated with interferon-alpha (IFNα + TKI) or had received IFNα treatment only (IFNα-only). The T/NK-cell subset distribution, NK- and T-cell cytokine production, activation and maturation markers were measured in 44 patients in DMR treated with IFNα only (9), with IFNα + TKI (11) and with TKI-only (24). IFNα + TKI and TKI-only groups were eligible to TKI discontinuation according to the NCCN and ESMO guidelines (stable MR4 for more than two years). In IFNα-treated patients, we documented an increased number of lymphocytes capable of producing IFNγ and TNFα compared to the TKI-only group. In INFα + TKI patients, the percentage of NKG2C expression and its mean fluorescence intensity were significantly higher compared to the TKI-only group and to the INFα-only group in the CD56dim/CD16+ NK cell subsets (INFα + TKI vs. TKI-only p = 0.041, p = 0.037; INFα + TKI vs. INFα-only p = 0.03, p = 0.033, respectively). Furthermore, in INFα-only treated patients, we observed an increase of NKp46 MFI in the CD56bright/CD16- NK cell subset that becomes significant compared to the INFα + TKI group (p = 0.008). Our data indicate that a previous exposure to IFNα substantially and persistently modified the immune system of CML patients in memory T lymphocytes, differentiated NKG2C+ “long-lived” NK cells responses, even years after the last IFNα contact.
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spelling pubmed-95708422022-10-17 Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation Puzzolo, Maria Cristina Breccia, Massimo Mariglia, Paola Colafigli, Gioia Pepe, Sara Scalzulli, Emilia Mariggiò, Elena Latagliata, Roberto Guarini, Anna Foà, Robin J Clin Med Article A deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR patients who had received TKI treatment only (TKI-only) or had been previously treated with interferon-alpha (IFNα + TKI) or had received IFNα treatment only (IFNα-only). The T/NK-cell subset distribution, NK- and T-cell cytokine production, activation and maturation markers were measured in 44 patients in DMR treated with IFNα only (9), with IFNα + TKI (11) and with TKI-only (24). IFNα + TKI and TKI-only groups were eligible to TKI discontinuation according to the NCCN and ESMO guidelines (stable MR4 for more than two years). In IFNα-treated patients, we documented an increased number of lymphocytes capable of producing IFNγ and TNFα compared to the TKI-only group. In INFα + TKI patients, the percentage of NKG2C expression and its mean fluorescence intensity were significantly higher compared to the TKI-only group and to the INFα-only group in the CD56dim/CD16+ NK cell subsets (INFα + TKI vs. TKI-only p = 0.041, p = 0.037; INFα + TKI vs. INFα-only p = 0.03, p = 0.033, respectively). Furthermore, in INFα-only treated patients, we observed an increase of NKp46 MFI in the CD56bright/CD16- NK cell subset that becomes significant compared to the INFα + TKI group (p = 0.008). Our data indicate that a previous exposure to IFNα substantially and persistently modified the immune system of CML patients in memory T lymphocytes, differentiated NKG2C+ “long-lived” NK cells responses, even years after the last IFNα contact. MDPI 2022-09-23 /pmc/articles/PMC9570842/ /pubmed/36233461 http://dx.doi.org/10.3390/jcm11195594 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Puzzolo, Maria Cristina
Breccia, Massimo
Mariglia, Paola
Colafigli, Gioia
Pepe, Sara
Scalzulli, Emilia
Mariggiò, Elena
Latagliata, Roberto
Guarini, Anna
Foà, Robin
Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title_full Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title_fullStr Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title_full_unstemmed Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title_short Immunomodulatory Effects of IFNα on T and NK Cells in Chronic Myeloid Leukemia Patients in Deep Molecular Response Preparing for Treatment Discontinuation
title_sort immunomodulatory effects of ifnα on t and nk cells in chronic myeloid leukemia patients in deep molecular response preparing for treatment discontinuation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570842/
https://www.ncbi.nlm.nih.gov/pubmed/36233461
http://dx.doi.org/10.3390/jcm11195594
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