Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance
IntroductionCD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with un...
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Frontiers Media S.A.
2025-02-01
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| author | Barbara Forró Béla Kajtár Ágnes Lacza László Kereskai Livia Vida Balázs Kőszegi Péter Urbán József Kun József Kun Attila Gyenesei Szabolcs Kosztolányi Dániel Kehl Pál Jáksó |
| author_facet | Barbara Forró Béla Kajtár Ágnes Lacza László Kereskai Livia Vida Balázs Kőszegi Péter Urbán József Kun József Kun Attila Gyenesei Szabolcs Kosztolányi Dániel Kehl Pál Jáksó |
| author_sort | Barbara Forró |
| collection | DOAJ |
| description | IntroductionCD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with untreated monoclonal gammopathy of undetermined significance (MGUS) and myeloma (MM). Despite the expanding literature data, the exact function of CD20+ T cells remains unclear.MethodsWe investigated the incidence of CD20+ T-cells in MGUS (n=27), and MM using a larger cohort (n=125) and compared it with control bone marrow samples (n=39). We examined their presence before and after treatment in 32 cases with flow cytometry. Comprehensive flow cytometric analysis included the examination of functional (T-cell activation, cytotoxic molecules and T-cell exhaustion) and maturation markers in a large number of cases. In addition RNA sequencing and subsequent bioinformatics analyses were carried out to detect differentially expressed (DE) genes of FACS sorted CD20+ T-cells versus CD20- T-cells.Results and discussionWe found that CD20+ T-cells are phenotypically and transcriptionally different from CD20- T-cells. Elevated incidence of CD20+ T-cells in MGUS and MM and the expression of CD8, NKG2D, and CD28 suggests anti-tumor functionality. Increased PD-1 expression indicates T-cell exhaustion which was mostly detected in the samples of patients with a higher tumor percentage. The majority of CD20+ T-cells are effector or effector memory T-cells. Some of the differentially expressed genes suggest antitumor function via regulating T-cell activation pathways, while other genes involved in tumor escape from immune surveillance by suppressing T-cells or by reprogramming T-cells toward T-cell exhaustion. Our findings suggest that CD20+ T-cells may play a vital role both in immune surveillance and immune escape contributing to progression of multiple myeloma. |
| format | Article |
| id | doaj-art-40f97795d75a437b9c8775b3368f7e08 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-40f97795d75a437b9c8775b3368f7e082025-08-20T02:03:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14649401464940Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significanceBarbara Forró0Béla Kajtár1Ágnes Lacza2László Kereskai3Livia Vida4Balázs Kőszegi5Péter Urbán6József Kun7József Kun8Attila Gyenesei9Szabolcs Kosztolányi10Dániel Kehl11Pál Jáksó12Department of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryDepartment of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryDepartment of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryDepartment of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryDepartment of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryDepartment of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, HungaryGenomics and Bioinformatics Core Facility, Szentágothai Research Centre of the University of Pécs, Pécs, HungaryGenomics and Bioinformatics Core Facility, Szentágothai Research Centre of the University of Pécs, Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, University of Pécs Medical School, Pécs, HungaryGenomics and Bioinformatics Core Facility, Szentágothai Research Centre of the University of Pécs, Pécs, Hungary1st Department of Internal Medicine, University of Pécs Medical School, Pécs, HungaryFaculty of Business and Economics, University of Pécs, Pécs, HungaryDepartment of Pathology, University of Pécs Medical School, Clinical Centre, Pécs, HungaryIntroductionCD20+ T-cells were described firstly in peripheral blood and later in bone marrow in patients with hematological tumors, and certain immune-mediated diseases. During our hematological diagnostic work, this peculiar subgroup of lymphocytes has been consistently observed associated with untreated monoclonal gammopathy of undetermined significance (MGUS) and myeloma (MM). Despite the expanding literature data, the exact function of CD20+ T cells remains unclear.MethodsWe investigated the incidence of CD20+ T-cells in MGUS (n=27), and MM using a larger cohort (n=125) and compared it with control bone marrow samples (n=39). We examined their presence before and after treatment in 32 cases with flow cytometry. Comprehensive flow cytometric analysis included the examination of functional (T-cell activation, cytotoxic molecules and T-cell exhaustion) and maturation markers in a large number of cases. In addition RNA sequencing and subsequent bioinformatics analyses were carried out to detect differentially expressed (DE) genes of FACS sorted CD20+ T-cells versus CD20- T-cells.Results and discussionWe found that CD20+ T-cells are phenotypically and transcriptionally different from CD20- T-cells. Elevated incidence of CD20+ T-cells in MGUS and MM and the expression of CD8, NKG2D, and CD28 suggests anti-tumor functionality. Increased PD-1 expression indicates T-cell exhaustion which was mostly detected in the samples of patients with a higher tumor percentage. The majority of CD20+ T-cells are effector or effector memory T-cells. Some of the differentially expressed genes suggest antitumor function via regulating T-cell activation pathways, while other genes involved in tumor escape from immune surveillance by suppressing T-cells or by reprogramming T-cells toward T-cell exhaustion. Our findings suggest that CD20+ T-cells may play a vital role both in immune surveillance and immune escape contributing to progression of multiple myeloma.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1464940/fullmultiple myelomaCD20T-cellstumor immunologyT-cell exhaustion |
| spellingShingle | Barbara Forró Béla Kajtár Ágnes Lacza László Kereskai Livia Vida Balázs Kőszegi Péter Urbán József Kun József Kun Attila Gyenesei Szabolcs Kosztolányi Dániel Kehl Pál Jáksó Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance Frontiers in Immunology multiple myeloma CD20 T-cells tumor immunology T-cell exhaustion |
| title | Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| title_full | Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| title_fullStr | Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| title_full_unstemmed | Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| title_short | Multiparameter flow cytometric and transcriptional analyis of CD20 positive T-cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| title_sort | multiparameter flow cytometric and transcriptional analyis of cd20 positive t cells in bone marrow in patients of multiple myeloma and monoclonal gammopathy of undetermined significance |
| topic | multiple myeloma CD20 T-cells tumor immunology T-cell exhaustion |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1464940/full |
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