CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression

Cristiana Rodrigues; Paula Laranjeira; Aryane Pinho; Isabel Silva; Sandra Silva; Margarida Coucelo; Ana Catarina Oliveira; Ana Teresa Simões; Inês Damásio; Helena Matos Silva; Mafalda Urbano; Ana Bela Sarmento-Ribeiro; Catarina Geraldes; M Rosário Domingues; Julia Almeida; Ignacio Criado; Alberto Orfao; Artur Paiva

doi:10.3389/fonc.2024.1380648

CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression

Front Oncol. 2024 Mar 28:14:1380648. doi: 10.3389/fonc.2024.1380648. eCollection 2024.

Authors

Cristiana Rodrigues^{1

2}, Paula Laranjeira^{1

3

4

5

6}, Aryane Pinho^{4

6

7}, Isabel Silva¹, Sandra Silva¹, Margarida Coucelo⁸, Ana Catarina Oliveira⁸, Ana Teresa Simões⁸, Inês Damásio⁹, Helena Matos Silva⁹, Mafalda Urbano¹⁰, Ana Bela Sarmento-Ribeiro^{3

4

5

10

11}, Catarina Geraldes^{3

4

5

10

11}, M Rosário Domingues^{12

13}, Julia Almeida^{14

15

16

17}, Ignacio Criado^{14

15

16

17}, Alberto Orfao^{14

15

16

17}, Artur Paiva^{1

3

4

5

18}

Affiliations

¹ Flow Cytometry Unit, Department of Clinical Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
² Department of Chemistry, University of Aveiro, Aveiro, Portugal.
³ Coimbra Institute for Clinical and Biomedical Research (iCBR), Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine (FMUC), University of Coimbra, Coimbra, Portugal.
⁴ Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.
⁵ Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
⁶ Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
⁷ Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
⁸ Unidade Funcional de Hematologia Molecular, Serviço de Hematologia Clínica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁹ Hematology Department, Centro Hospitalar Tondela-Viseu, Viseu, Portugal.
¹⁰ Hematology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
¹¹ University Clinics of Hematology and Oncology and Laboratory of Oncobiology and Hematology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
¹² Mass Spectrometry Centre, Associated Laboratory for Green Chemistry (LAQV-REQUIMTE), Department of Chemistry, University of Aveiro, Aveiro, Portugal.
¹³ CESAM-Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
¹⁴ Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC-University of Salamanca), Salamanca, Spain.
¹⁵ Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain.
¹⁶ Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
¹⁷ Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
¹⁸ Ciências Biomédicas Laboratoriais, Instituto Politécnico de Coimbra, Escola Superior de Tecnologia da Saúde de Coimbra (ESTESC)-Coimbra Health School, Coimbra, Portugal.

Abstract

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer.

Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease.

Results and discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vβ 5.1 in CD4+ CD20+ T cells in CLL.

Keywords: CD20+ T cells; T cell polarization; chronic lymphocytic leukemia; immunoglobulin heavy chain variable region; monoclonal B lymphocytosis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the 0639-IDIAL-NET-3-3 grant (INTERREG POCTEP Spain-Portugal) from the European Regional Development Fund, and by the “Early Cancer Research Initiative Network on MBL (ECRINM3)” ACCELERATOR award (CRUK -UK-, Fundación AECC -Spain- and Associazione Italiana per la Ricerca Sul Cancro -Italy).