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Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α

2020-01-03Journal article Open access
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dc.contributor.authorAlves, Raquel
dc.contributor.authorMcArdle, Stephanie E. B.
dc.contributor.authorVadakekolathu, Jayakumar
dc.contributor.authorGonçalves, Ana Cristina
dc.contributor.authorFreitas-Tavares, Paulo
dc.contributor.authorPereira, Amélia
dc.contributor.authorAlmeida, Antonio M.
dc.contributor.authorSarmento-Ribeiro, Ana Bela
dc.contributor.authorRutella, Sergio
dc.date.accessioned2021-03-20T16:35:04Z
dc.date.available2021-03-20T16:35:04Z
dc.date.issued2020-01-03
dc.description.abstractBACKGROUND: Tumor cells have evolved complex strategies to escape immune surveillance, a process which involves NK cells and T lymphocytes, and various immunological factors. Indeed, tumor cells recruit immunosuppressive cells [including regulatory T-cells (Treg), myeloid-derived suppressor cells (MDSC)] and express factors such as PD-L1. Molecularly targeted therapies, such as imatinib, have off-target effects that may influence immune function. Imatinib has been shown to modulate multiple cell types involved in anti-cancer immune surveillance, with potentially detrimental or favorable outcomes. Imatinib and other tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) have dramatically changed disease course. Our study aimed to characterize the different populations of the immune system in patients with CML affected by their treatment. METHODS: Forty-one patients with CML [33 treated with TKIs and 8 with TKIs plus interferon (IFN)-α] and 20 controls were enrolled in the present study. Peripheral blood populations of the immune system [referred to as the overview of immune system (OVIS) panel, Treg cells and MDSCs] and PD-1 expression were evaluated by flow cytometry. The immunological profile was assessed using the mRNA Pan-Cancer Immune Profiling Panel and a NanoString nCounter FLEX platform. RESULTS: Patients receiving combination therapy (TKIs + IFN-α) had lower numbers of lymphocytes, particularly T cells [838/µL (95% CI 594-1182)] compared with healthy controls [1500/µL (95% CI 1207 - 1865), p = 0.017]. These patients also had a higher percentage of Treg (9.1%) and CD4+PD-1+ cells (1.65%) compared with controls [Treg (6.1%) and CD4+/PD-1+(0.8%); p ≤ 0.05]. Moreover, patients treated with TKIs had more Mo-MDSCs (12.7%) whereas those treated with TKIs + IFN-α had more Gr-MDSC (21.3%) compared to controls [Mo-MDSC (11.4%) and Gr-MDSC (8.48%); p ≤ 0.05]. CD56bright NK cells, a cell subset endowed with immune-regulatory properties, were increased in patients receiving TKIs plus IFN-α compared with those treated with TKIs alone. Interestingly, serum IL-21 was significantly lower in the TKIs plus IFN-α cohort. Within the group of patients treated with TKI monotherapy, we observed that individuals receiving 2nd generation TKIs had lower percentages of CD4+ Treg (3.63%) and Gr-MDSC (4.2%) compared to patients under imatinib treatment (CD4+ Treg 6.18% and Gr-MDSC 8.2%), but higher levels of PD-1-co-expressing CD4+ cells (1.92%). CONCLUSIONS: Our results suggest that TKIs in combination with IFN-α may promote an enhanced immune suppressive state.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1186/s12967-019-02194-xpt_PT
dc.identifier.eid85077479879
dc.identifier.issn1479-5876
dc.identifier.pmcPMC6941328
dc.identifier.pmid31900171
dc.identifier.urihttp://hdl.handle.net/10400.14/32300
dc.identifier.wos000513264900001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectChronic myeloid leukemiapt_PT
dc.subjectGene expression profilingpt_PT
dc.subjectImmune monitoringpt_PT
dc.subjectImmunotherapypt_PT
dc.subjectInterferonpt_PT
dc.titleFlow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-αpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleJournal of Translational Medicinept_PT
oaire.citation.volume18pt_PT
person.familyNameAlves
person.familyNameMcArdle
person.familyNameVadakekolathu
person.familyNameGonçalves
person.familyNameTavares
person.familyNameAlmeida
person.familyNameSarmento Ribeiro
person.familyNameRutella
person.givenNameRaquel
person.givenNameStephanie
person.givenNameJayakumar
person.givenNameAna Cristina
person.givenNamePaulo
person.givenNameAntónio
person.givenNameAna Bela
person.givenNameSergio
person.identifierR-000-0QS
person.identifier823829
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person.identifier.orcid0000-0003-4361-0928
person.identifier.orcid0000-0002-4142-4841
person.identifier.orcid0000-0003-1970-7375
person.identifier.ridV-2781-2017
person.identifier.ridI-4712-2015
person.identifier.ridV-2202-2017
person.identifier.ridU-9773-2017
person.identifier.scopus-author-id55656424100
person.identifier.scopus-author-id6603705599
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person.identifier.scopus-author-id36096765300
person.identifier.scopus-author-id20936340000
person.identifier.scopus-author-id7202913805
person.identifier.scopus-author-id8444018600
person.identifier.scopus-author-id7004418747
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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