Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma
Despite recent advances, Multiple Myeloma (MM) remains an incurable disease with apparent heterogeneity that may explain patients’ variable clinical outcomes. While the phenotypic, (epi)genetic, and molecular characteristics of myeloma cells have been thoroughly examined, there is limited informatio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3245 |
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doaj-2434f00a2bab479eb4209abf724bc4f3 |
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| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Konstantinos Papadimitriou Nikolaos Tsakirakis Panagiotis Malandrakis Panagiotis Vitsos Andreas Metousis Nikolaos Orologas-Stavrou Ioannis Ntanasis-Stathopoulos Nikolaos Kanellias Evangelos Eleutherakis-Papaiakovou Panagiotis Pothos Despina Fotiou Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos Evangelos Terpos Ourania E. Tsitsilonis Ioannis V. Kostopoulos |
| spellingShingle |
Konstantinos Papadimitriou Nikolaos Tsakirakis Panagiotis Malandrakis Panagiotis Vitsos Andreas Metousis Nikolaos Orologas-Stavrou Ioannis Ntanasis-Stathopoulos Nikolaos Kanellias Evangelos Eleutherakis-Papaiakovou Panagiotis Pothos Despina Fotiou Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos Evangelos Terpos Ourania E. Tsitsilonis Ioannis V. Kostopoulos Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma Cancers multiple myeloma bone marrow microenvironment immune profiling immune signatures minimal residual disease |
| author_facet |
Konstantinos Papadimitriou Nikolaos Tsakirakis Panagiotis Malandrakis Panagiotis Vitsos Andreas Metousis Nikolaos Orologas-Stavrou Ioannis Ntanasis-Stathopoulos Nikolaos Kanellias Evangelos Eleutherakis-Papaiakovou Panagiotis Pothos Despina Fotiou Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos Evangelos Terpos Ourania E. Tsitsilonis Ioannis V. Kostopoulos |
| author_sort |
Konstantinos Papadimitriou |
| title |
Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma |
| title_short |
Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma |
| title_full |
Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma |
| title_fullStr |
Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma |
| title_full_unstemmed |
Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple Myeloma |
| title_sort |
deep phenotyping reveals distinct immune signatures correlating with prognostication, treatment responses, and mrd status in multiple myeloma |
| publisher |
MDPI AG |
| series |
Cancers |
| issn |
2072-6694 |
| publishDate |
2020-11-01 |
| description |
Despite recent advances, Multiple Myeloma (MM) remains an incurable disease with apparent heterogeneity that may explain patients’ variable clinical outcomes. While the phenotypic, (epi)genetic, and molecular characteristics of myeloma cells have been thoroughly examined, there is limited information regarding the role of the bone marrow (BM) microenvironment in the natural history of the disease. In the present study, we performed deep phenotyping of 32 distinct immune cell subsets in a cohort of 94 MM patients to reveal unique immune profiles in both BM and peripheral blood (PB) that characterize distinct prognostic groups, responses to induction treatment, and minimal residual disease (MRD) status. Our data show that PB cells do not reflect the BM microenvironment and that the two sites should be studied independently. Adverse ISS stage and high-risk cytogenetics were correlated with distinct immune profiles; most importantly, BM signatures comprised decreased tumor-associated macrophages (TAMs) and erythroblasts, whereas the unique Treg signatures in PB could discriminate those patients achieving complete remission after VRd induction therapy. Moreover, MRD negative status was correlated with a more experienced CD4- and CD8-mediated immunity phenotype in both BM and PB, thus highlighting a critical role of by-stander cells linked to MRD biology. |
| topic |
multiple myeloma bone marrow microenvironment immune profiling immune signatures minimal residual disease |
| url |
https://www.mdpi.com/2072-6694/12/11/3245 |
| work_keys_str_mv |
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doaj-2434f00a2bab479eb4209abf724bc4f32020-11-25T04:06:53ZengMDPI AGCancers2072-66942020-11-01123245324510.3390/cancers12113245Deep Phenotyping Reveals Distinct Immune Signatures Correlating with Prognostication, Treatment Responses, and MRD Status in Multiple MyelomaKonstantinos Papadimitriou0Nikolaos Tsakirakis1Panagiotis Malandrakis2Panagiotis Vitsos3Andreas Metousis4Nikolaos Orologas-Stavrou5Ioannis Ntanasis-Stathopoulos6Nikolaos Kanellias7Evangelos Eleutherakis-Papaiakovou8Panagiotis Pothos9Despina Fotiou10Maria Gavriatopoulou11Efstathios Kastritis12Meletios-Athanasios Dimopoulos13Evangelos Terpos14Ourania E. Tsitsilonis15Ioannis V. Kostopoulos16Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDepartment of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, GreeceDespite recent advances, Multiple Myeloma (MM) remains an incurable disease with apparent heterogeneity that may explain patients’ variable clinical outcomes. While the phenotypic, (epi)genetic, and molecular characteristics of myeloma cells have been thoroughly examined, there is limited information regarding the role of the bone marrow (BM) microenvironment in the natural history of the disease. In the present study, we performed deep phenotyping of 32 distinct immune cell subsets in a cohort of 94 MM patients to reveal unique immune profiles in both BM and peripheral blood (PB) that characterize distinct prognostic groups, responses to induction treatment, and minimal residual disease (MRD) status. Our data show that PB cells do not reflect the BM microenvironment and that the two sites should be studied independently. Adverse ISS stage and high-risk cytogenetics were correlated with distinct immune profiles; most importantly, BM signatures comprised decreased tumor-associated macrophages (TAMs) and erythroblasts, whereas the unique Treg signatures in PB could discriminate those patients achieving complete remission after VRd induction therapy. Moreover, MRD negative status was correlated with a more experienced CD4- and CD8-mediated immunity phenotype in both BM and PB, thus highlighting a critical role of by-stander cells linked to MRD biology.https://www.mdpi.com/2072-6694/12/11/3245multiple myelomabone marrow microenvironmentimmune profilingimmune signaturesminimal residual disease |