Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107612 https://doi.org/10.3389/fimmu.2018.02587 |
Resumo: | Natural killer (NK) cells are a very important component of the innate immune response involved in the lysis of virus infected and tumor cells. Aging has a profound impact in the frequency, phenotype and function of NK cells. Chronic Myeloid Leukemia (CML) is caused by the BCR-ABL gene formation encoding aberrant oncoprotein tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) induces durable deep molecular response. The response to treatment and life expectancy is lower in older patients with chronic phase of CML than in younger patients. In this work we analyse NK cells from TKI-treated CML patients and healthy controls stratified according to age. We have analyzed the expression of NK receptors, activation markers, NK cell differentiation in CD56bright and CD56dim NK cell subsets and the expression of CD107a and IFN-γ in NK cells stimulated with K562. Whereas significant differences on the phenotype and function of NK cells were found between middle-aged (35-65 years old) and elderly (older than 65) healthy individuals, NK cells from TKI-treated CML patients do not show significant differences related with age in most parameters studied, indicating that age is not a limitation of the NK cell recovery after treatment with TKI. Our results also revealed differences in the expression of NK receptors, activation markers and functional assays in NK cells from TKI-treated CML patients compared with age-matched healthy controls. These results highlight the relevance of NK cells in TKI-treated patients and the need of an extensive analysis of the effect of aging on NK cell phenotype and function in these patients in order to define new NK-cell based strategies directed to control CML progression and achieve long-term disease remission after TKI cessation. |
id |
RCAP_8f3179a5baaf51be561efec0a3ac5faf |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/107612 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase InhibitorsagingCMLNK receptorsactivation markersdifferentiation markerscytokinesNK cell subsetstyrosine kinase inhibitorsAdultAgedAged, 80 and overAgingAntineoplastic AgentsCell DifferentiationFemaleGenes, ablHumansK562 CellsKiller Cells, NaturalLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLymphocyte ActivationMaleMiddle AgedProtein Kinase InhibitorsTreatment OutcomeAge FactorsNatural killer (NK) cells are a very important component of the innate immune response involved in the lysis of virus infected and tumor cells. Aging has a profound impact in the frequency, phenotype and function of NK cells. Chronic Myeloid Leukemia (CML) is caused by the BCR-ABL gene formation encoding aberrant oncoprotein tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) induces durable deep molecular response. The response to treatment and life expectancy is lower in older patients with chronic phase of CML than in younger patients. In this work we analyse NK cells from TKI-treated CML patients and healthy controls stratified according to age. We have analyzed the expression of NK receptors, activation markers, NK cell differentiation in CD56bright and CD56dim NK cell subsets and the expression of CD107a and IFN-γ in NK cells stimulated with K562. Whereas significant differences on the phenotype and function of NK cells were found between middle-aged (35-65 years old) and elderly (older than 65) healthy individuals, NK cells from TKI-treated CML patients do not show significant differences related with age in most parameters studied, indicating that age is not a limitation of the NK cell recovery after treatment with TKI. Our results also revealed differences in the expression of NK receptors, activation markers and functional assays in NK cells from TKI-treated CML patients compared with age-matched healthy controls. These results highlight the relevance of NK cells in TKI-treated patients and the need of an extensive analysis of the effect of aging on NK cell phenotype and function in these patients in order to define new NK-cell based strategies directed to control CML progression and achieve long-term disease remission after TKI cessation.Frontiers Media S.A.2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107612http://hdl.handle.net/10316/107612https://doi.org/10.3389/fimmu.2018.02587eng1664-3224Rodrigues-Santos, PauloLópez-Sejas, NelsonAlmeida, Jani-SofiaRuzičková, LenkaCouceiro, PatríciaAlves, VeraCampos, CarmenAlonso, CoronaTarazona, RaquelFreitas-Tavares, PauloSolana, RafaelSantos-Rosa, Manuelinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T09:52:27Zoai:estudogeral.uc.pt:10316/107612Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:56.787158Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
title |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
spellingShingle |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors Rodrigues-Santos, Paulo aging CML NK receptors activation markers differentiation markers cytokines NK cell subsets tyrosine kinase inhibitors Adult Aged Aged, 80 and over Aging Antineoplastic Agents Cell Differentiation Female Genes, abl Humans K562 Cells Killer Cells, Natural Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphocyte Activation Male Middle Aged Protein Kinase Inhibitors Treatment Outcome Age Factors |
title_short |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
title_full |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
title_fullStr |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
title_full_unstemmed |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
title_sort |
Effect of Age on NK Cell Compartment in Chronic Myeloid Leukemia Patients Treated With Tyrosine Kinase Inhibitors |
author |
Rodrigues-Santos, Paulo |
author_facet |
Rodrigues-Santos, Paulo López-Sejas, Nelson Almeida, Jani-Sofia Ruzičková, Lenka Couceiro, Patrícia Alves, Vera Campos, Carmen Alonso, Corona Tarazona, Raquel Freitas-Tavares, Paulo Solana, Rafael Santos-Rosa, Manuel |
author_role |
author |
author2 |
López-Sejas, Nelson Almeida, Jani-Sofia Ruzičková, Lenka Couceiro, Patrícia Alves, Vera Campos, Carmen Alonso, Corona Tarazona, Raquel Freitas-Tavares, Paulo Solana, Rafael Santos-Rosa, Manuel |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Rodrigues-Santos, Paulo López-Sejas, Nelson Almeida, Jani-Sofia Ruzičková, Lenka Couceiro, Patrícia Alves, Vera Campos, Carmen Alonso, Corona Tarazona, Raquel Freitas-Tavares, Paulo Solana, Rafael Santos-Rosa, Manuel |
dc.subject.por.fl_str_mv |
aging CML NK receptors activation markers differentiation markers cytokines NK cell subsets tyrosine kinase inhibitors Adult Aged Aged, 80 and over Aging Antineoplastic Agents Cell Differentiation Female Genes, abl Humans K562 Cells Killer Cells, Natural Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphocyte Activation Male Middle Aged Protein Kinase Inhibitors Treatment Outcome Age Factors |
topic |
aging CML NK receptors activation markers differentiation markers cytokines NK cell subsets tyrosine kinase inhibitors Adult Aged Aged, 80 and over Aging Antineoplastic Agents Cell Differentiation Female Genes, abl Humans K562 Cells Killer Cells, Natural Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphocyte Activation Male Middle Aged Protein Kinase Inhibitors Treatment Outcome Age Factors |
description |
Natural killer (NK) cells are a very important component of the innate immune response involved in the lysis of virus infected and tumor cells. Aging has a profound impact in the frequency, phenotype and function of NK cells. Chronic Myeloid Leukemia (CML) is caused by the BCR-ABL gene formation encoding aberrant oncoprotein tyrosine kinase. Treatment with tyrosine kinase inhibitors (TKIs) induces durable deep molecular response. The response to treatment and life expectancy is lower in older patients with chronic phase of CML than in younger patients. In this work we analyse NK cells from TKI-treated CML patients and healthy controls stratified according to age. We have analyzed the expression of NK receptors, activation markers, NK cell differentiation in CD56bright and CD56dim NK cell subsets and the expression of CD107a and IFN-γ in NK cells stimulated with K562. Whereas significant differences on the phenotype and function of NK cells were found between middle-aged (35-65 years old) and elderly (older than 65) healthy individuals, NK cells from TKI-treated CML patients do not show significant differences related with age in most parameters studied, indicating that age is not a limitation of the NK cell recovery after treatment with TKI. Our results also revealed differences in the expression of NK receptors, activation markers and functional assays in NK cells from TKI-treated CML patients compared with age-matched healthy controls. These results highlight the relevance of NK cells in TKI-treated patients and the need of an extensive analysis of the effect of aging on NK cell phenotype and function in these patients in order to define new NK-cell based strategies directed to control CML progression and achieve long-term disease remission after TKI cessation. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107612 http://hdl.handle.net/10316/107612 https://doi.org/10.3389/fimmu.2018.02587 |
url |
http://hdl.handle.net/10316/107612 https://doi.org/10.3389/fimmu.2018.02587 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1664-3224 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134125237469184 |