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Title: NKT-Like (CD3+CD56+) Cells in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors
Authors: Almeida, Jani Sofia 
Couceiro, Patrícia 
López-Sejas, Nelson
Alves, Vera 
Růžičková, Lenka
Tarazona, Raquel
Solana, Rafael
Tavares, Paulo 
Santos Rosa, Manuel 
Rodrigues-Santos, Paulo 
Keywords: chronic myeloid leukemia; tyrosine kinase inhibitors; NKT-like cells; natural cytotoxicity receptors; immune checkpoints
Issue Date: 2019
Publisher: Frontiers Media S.A.
Project: This work was supported by the FEDER Funds through the Operational Program Competitiveness Factors—COMPETE 2020 and by National Funds through the FCT-Foundation for Science and Technology within the framework of the Strategic Project with reference assigned by COMPETE: POCI-01-0145- FEDER-007440 (to PR-S) and by the program Iberoamerica Scholarships: Santander Research/Santander Universities 2016- 2017 (to NL-S). This work was also supported by grants PI13/02691 and PI16/01615 (to RS) from Spanish Ministry of Health, SAF2017-87538-R (to RT) fromthe Ministry of Economy and Competitiveness of Spain and IB16164 and R18085 from Junta de Extremadura (to RT) co-financed by European Regional Development Funds. 
Serial title, monograph or event: Frontiers in Immunology
Volume: 10
Abstract: Therapy with Tyrosine Kinase Inhibitors (TKI) aiming stable deep molecular response is the gold standard to treat Chronic Myeloid Leukemia (CML). NKT-like cells (CD3+CD56+) combine characteristics of T and NK cells. The physiopathological role of these cells remains unknown although the literature refers their association with inflammation, autoimmune diseases, and cancer. Since the information regarding the role of NKT-like cells in CML is rare, we aimed at the characterization of these cells in CML patients treated with TKIs. Peripheral blood NKT-like cells from 48 CML patients and 40 healthy donors were analyzed by multiparametric flow cytometry. Functional tests consisting of co-culture with leukemic target cells (K562 cell line) were used to measure degranulation and cytokine production. Our results revealed that NKT-like cells are decreased in treated CML patients, although they present increased expression of activation markers (CD69 and HLA-DR), increased degranulation (CD107a) and impaired IFN-γ production. Significantly alterations on the expression of tumor recognition (NCRs and NKp80), and immune regulation receptors (LAG-3, TIM-3, and CD137) by NKT-like cells were observed in CML patients. Second generation TKIs increased cell activation (CD69) and decreased expression of NKp44 and NKp80 by NKT-like cells from CML patients when compared to Imatinib. CML patients that achieved deep molecular response (MR4.5) presented downregulation of NKp44 and LAG-3. Further studies are needed to clarify the role of these cells as biomarkers of therapy response and also to evaluate their value for discrimination of better candidates for sustained treatment-free remission after TKI discontinuation.
ISSN: 1664-3224
DOI: 10.3389/fimmu.2019.02493
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais

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