The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial
Treatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Tri...
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2025-04-01
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| author | María Belén Sanchez Bianca Vasconcelos Cordoba Carolina Pavlovsky Beatriz Moiraghi Ana Ines Varela Isabel Giere Mariana Juni Nicolas Flaibani José Mordoh Julio Cesar Sanchez Avalos Estrella Mariel Levy Michele Bianchini |
| author_facet | María Belén Sanchez Bianca Vasconcelos Cordoba Carolina Pavlovsky Beatriz Moiraghi Ana Ines Varela Isabel Giere Mariana Juni Nicolas Flaibani José Mordoh Julio Cesar Sanchez Avalos Estrella Mariel Levy Michele Bianchini |
| author_sort | María Belén Sanchez |
| collection | DOAJ |
| description | Treatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Trial (AST), including 46 patients in 2019 (AST I) and 35 new patients between 2022 and 2023 (AST II). To characterize NK cell subsets in patients attempting TFR, peripheral blood mononuclear cell samples were collected before stopping treatment and phenotype and functional characteristics were assessed by flow cytometry. Non-relapsing patients from AST I exhibited NK cell subpopulations with cytomegalovirus-related memory features, high expression of cytotoxicity markers, and robust functionality. Remarkably, though clinical variables were very similar between cohorts, significant immune differences were observed. NK cell percentage and CD16 and CD57 receptor expression levels were significantly reduced in AST II (<i>p</i> = 0.0051; <i>p</i> = 0.0222; <i>p</i> = 0.0033, respectively), whereas NKp46, NKp44 and PD-1 expression levels were significantly increased (<i>p</i> = 0.0081; <i>p</i> < 0.0001; <i>p</i> < 0.0001, respectively). NK cells from AST II patients demonstrated higher overall functionality and more memory-like subpopulations, characterized mainly by the expression of CD57, NKG2C, NKp30 and NKp46 receptors among CD56<sup>dim</sup> NK cells, also with enhanced functional performance. However, in AST II, we were unable to report an association with clinical outcome. Given the enrollment time of both cohorts and that they appear to be clinically homogeneous, we consider that COVID could be impacting the immune landscape; accordingly, serum samples from AST II, but not AST I, confirmed the presence of anti-SARS-CoV-2 IgG. The influence of the COVID pandemic and the different vaccine platforms on NK cells cannot be underestimated when evaluating the role of the immune system in cancer. |
| format | Article |
| id | doaj-art-75940c5aa1e14631b6a4fcba8bd3a1b7 |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-75940c5aa1e14631b6a4fcba8bd3a1b72025-08-20T02:58:47ZengMDPI AGCells2073-44092025-04-0114962810.3390/cells14090628The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop TrialMaría Belén Sanchez0Bianca Vasconcelos Cordoba1Carolina Pavlovsky2Beatriz Moiraghi3Ana Ines Varela4Isabel Giere5Mariana Juni6Nicolas Flaibani7José Mordoh8Julio Cesar Sanchez Avalos9Estrella Mariel Levy10Michele Bianchini11Centro de Investigaciones Oncológicas–Fundación Cáncer FUCA, Buenos Aires 1426, ArgentinaCentro de Investigaciones Oncológicas–Fundación Cáncer FUCA, Buenos Aires 1426, ArgentinaFundación para Combatir la Leucemia (FUNDALEU), Buenos Aires 1114, ArgentinaHospital José María Ramos Mejía, Buenos Aires 1221, ArgentinaHospital José María Ramos Mejía, Buenos Aires 1221, ArgentinaFundación para Combatir la Leucemia (FUNDALEU), Buenos Aires 1114, ArgentinaFundación para Combatir la Leucemia (FUNDALEU), Buenos Aires 1114, ArgentinaLaboratorio de Evolución, Facultad de Ciencias Exactas y Naturales (FCEN-UBA), Instituto de Genética, Ecología y Evolución de Buenos Aires (IEGEBA), Buenos Aires 1428, ArgentinaCentro de Investigaciones Oncológicas–Fundación Cáncer FUCA, Buenos Aires 1426, ArgentinaInstituto Alexander Fleming, Buenos Aires 1426, ArgentinaCentro de Investigaciones Oncológicas–Fundación Cáncer FUCA, Buenos Aires 1426, ArgentinaCentro de Investigaciones Oncológicas–Fundación Cáncer FUCA, Buenos Aires 1426, ArgentinaTreatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Trial (AST), including 46 patients in 2019 (AST I) and 35 new patients between 2022 and 2023 (AST II). To characterize NK cell subsets in patients attempting TFR, peripheral blood mononuclear cell samples were collected before stopping treatment and phenotype and functional characteristics were assessed by flow cytometry. Non-relapsing patients from AST I exhibited NK cell subpopulations with cytomegalovirus-related memory features, high expression of cytotoxicity markers, and robust functionality. Remarkably, though clinical variables were very similar between cohorts, significant immune differences were observed. NK cell percentage and CD16 and CD57 receptor expression levels were significantly reduced in AST II (<i>p</i> = 0.0051; <i>p</i> = 0.0222; <i>p</i> = 0.0033, respectively), whereas NKp46, NKp44 and PD-1 expression levels were significantly increased (<i>p</i> = 0.0081; <i>p</i> < 0.0001; <i>p</i> < 0.0001, respectively). NK cells from AST II patients demonstrated higher overall functionality and more memory-like subpopulations, characterized mainly by the expression of CD57, NKG2C, NKp30 and NKp46 receptors among CD56<sup>dim</sup> NK cells, also with enhanced functional performance. However, in AST II, we were unable to report an association with clinical outcome. Given the enrollment time of both cohorts and that they appear to be clinically homogeneous, we consider that COVID could be impacting the immune landscape; accordingly, serum samples from AST II, but not AST I, confirmed the presence of anti-SARS-CoV-2 IgG. The influence of the COVID pandemic and the different vaccine platforms on NK cells cannot be underestimated when evaluating the role of the immune system in cancer.https://www.mdpi.com/2073-4409/14/9/628NK cellsCOVIDchronic myeloid leukemiatreatment-free remission |
| spellingShingle | María Belén Sanchez Bianca Vasconcelos Cordoba Carolina Pavlovsky Beatriz Moiraghi Ana Ines Varela Isabel Giere Mariana Juni Nicolas Flaibani José Mordoh Julio Cesar Sanchez Avalos Estrella Mariel Levy Michele Bianchini The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial Cells NK cells COVID chronic myeloid leukemia treatment-free remission |
| title | The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial |
| title_full | The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial |
| title_fullStr | The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial |
| title_full_unstemmed | The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial |
| title_short | The Influence of the COVID-19 Pandemic in NK Cell Subpopulations from CML Patients Enrolled in the Argentina Stop Trial |
| title_sort | influence of the covid 19 pandemic in nk cell subpopulations from cml patients enrolled in the argentina stop trial |
| topic | NK cells COVID chronic myeloid leukemia treatment-free remission |
| url | https://www.mdpi.com/2073-4409/14/9/628 |
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