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T Cells In Chronic Lymphocytic Leukemia Display Dysregulated Expression Of Immune Checkpoints And Activation Markers
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Stockholm, Sweden.
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Stockholm, Sweden; Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Stockholm, Sweden.
Karolinska Inst, Canc Ctr Karolinska, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Stockholm, Sweden.
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 3, p. 562-572Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3+ cells and the CD8+ subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4+ and CD8+ cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients (P=0.0003 and P=0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4+ and CD8+ subsets, with a significantly higher PD-1 expression. Higher numbers of CD4+ and CD8+ cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67+) and activated (CD69+) CD4+ and CD8+ cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls (P<0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways.

Place, publisher, year, edition, pages
2017. Vol. 102, no 3, p. 562-572
Keywords [en]
SURFACE EXPRESSION; PERIPHERAL-BLOOD; CD152 CTLA-4; CLL PATIENTS; B-CLL; EXPANSION; SUBSETS; STAGE; PD-1; LENALIDOMIDE
National Category
Hematology
Research subject
Molecular Medicine
Identifiers
URN: urn:nbn:se:uu:diva-318346DOI: 10.3324/haematol.2016.151100ISI: 000402485700031PubMedID: 27927767OAI: oai:DiVA.org:uu-318346DiVA, id: diva2:1084357
Funder
Swedish Cancer SocietySwedish Research CouncilCancer and Allergy FoundationAvailable from: 2017-03-24 Created: 2017-03-24 Last updated: 2018-01-03Bibliographically approved

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