PROGRAMMED CELL DEATH PROTEIN 1 (PD-1) DOWNREGULATION ON REGULATORY T CELLS DURING TYROSINE KINASE INHIBITOR THERAPY IN CHRONIC MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Rodrigues-Santos P. 06/09/16; 132640; E1091
Dr. Paulo Rodrigues-Santos
Contributions
Contributions
Abstract
Abstract: E1091
Type: Eposter Presentation
Background
Programmed death-1 (PD-1) receptor and its ligands (PD-L1 and PD-L2) are involved in attenuating tumor immunity and facilitating tumor progression. PD-1, PD-L1 and PD-L2 therapeutic blocking agents have been reported to have significant antitumor effects. In chronic myeloid leukemia (CML), the expression of this receptor and its ligands is not fully characterized for the different subsets of cells of the immune system in which their expression is found constitutively or post-induction.
Aims
In this study, we analyzed the expression of PD-1 and its ligands on regulatory T cells (Tregs) in chronic phase CML patients to understand the mechanisms underlying suppressor effects that inhibit the anti-leukemia immune response.
Methods
Peripheral blood samples from chronic phase CML patients (n=50) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of regulatory T cells and surface expression of PD-1. Buffy coats (n=13) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®). Gene expression analysis and miRNA profiling were also performed for these samples.
Results
PD-1 Tregs were found significantly decreased (p<0.0001) in CML patients and down-regulation of this receptor was also observed (p<0.01). Naïve and memory Treg subsets were equally affected. No significant alterations were observed for PD-L1 and PD-L2 ligands. Although TGF-β and IL-10 production were not significantly altered by down-regulation of PD-1 in Tregs, the overall effect of tyrosine kinase inhibitor (TKI) therapy suggests a negative impact in these cells concerning the anti-leukemic immune response.
Conclusion
Regulatory T cells represent a major population of suppressors in the immune response against leukemia. Down-regulation of PD-1 receptor in Tregs during chronic phase CML reinforces the notion that discontinuation of treatment must be carefully evaluated beforehand, since these suppressor cells could permit the proliferation of existent residual leukemic cells.
Session topic: E-poster
Keyword(s): Immune response, T regulatory cells, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Programmed death-1 (PD-1) receptor and its ligands (PD-L1 and PD-L2) are involved in attenuating tumor immunity and facilitating tumor progression. PD-1, PD-L1 and PD-L2 therapeutic blocking agents have been reported to have significant antitumor effects. In chronic myeloid leukemia (CML), the expression of this receptor and its ligands is not fully characterized for the different subsets of cells of the immune system in which their expression is found constitutively or post-induction.
Aims
In this study, we analyzed the expression of PD-1 and its ligands on regulatory T cells (Tregs) in chronic phase CML patients to understand the mechanisms underlying suppressor effects that inhibit the anti-leukemia immune response.
Methods
Peripheral blood samples from chronic phase CML patients (n=50) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of regulatory T cells and surface expression of PD-1. Buffy coats (n=13) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®). Gene expression analysis and miRNA profiling were also performed for these samples.
Results
PD-1 Tregs were found significantly decreased (p<0.0001) in CML patients and down-regulation of this receptor was also observed (p<0.01). Naïve and memory Treg subsets were equally affected. No significant alterations were observed for PD-L1 and PD-L2 ligands. Although TGF-β and IL-10 production were not significantly altered by down-regulation of PD-1 in Tregs, the overall effect of tyrosine kinase inhibitor (TKI) therapy suggests a negative impact in these cells concerning the anti-leukemic immune response.
Conclusion
Regulatory T cells represent a major population of suppressors in the immune response against leukemia. Down-regulation of PD-1 receptor in Tregs during chronic phase CML reinforces the notion that discontinuation of treatment must be carefully evaluated beforehand, since these suppressor cells could permit the proliferation of existent residual leukemic cells.
Session topic: E-poster
Keyword(s): Immune response, T regulatory cells, Tyrosine kinase inhibitor
Abstract: E1091
Type: Eposter Presentation
Background
Programmed death-1 (PD-1) receptor and its ligands (PD-L1 and PD-L2) are involved in attenuating tumor immunity and facilitating tumor progression. PD-1, PD-L1 and PD-L2 therapeutic blocking agents have been reported to have significant antitumor effects. In chronic myeloid leukemia (CML), the expression of this receptor and its ligands is not fully characterized for the different subsets of cells of the immune system in which their expression is found constitutively or post-induction.
Aims
In this study, we analyzed the expression of PD-1 and its ligands on regulatory T cells (Tregs) in chronic phase CML patients to understand the mechanisms underlying suppressor effects that inhibit the anti-leukemia immune response.
Methods
Peripheral blood samples from chronic phase CML patients (n=50) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of regulatory T cells and surface expression of PD-1. Buffy coats (n=13) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®). Gene expression analysis and miRNA profiling were also performed for these samples.
Results
PD-1 Tregs were found significantly decreased (p<0.0001) in CML patients and down-regulation of this receptor was also observed (p<0.01). Naïve and memory Treg subsets were equally affected. No significant alterations were observed for PD-L1 and PD-L2 ligands. Although TGF-β and IL-10 production were not significantly altered by down-regulation of PD-1 in Tregs, the overall effect of tyrosine kinase inhibitor (TKI) therapy suggests a negative impact in these cells concerning the anti-leukemic immune response.
Conclusion
Regulatory T cells represent a major population of suppressors in the immune response against leukemia. Down-regulation of PD-1 receptor in Tregs during chronic phase CML reinforces the notion that discontinuation of treatment must be carefully evaluated beforehand, since these suppressor cells could permit the proliferation of existent residual leukemic cells.
Session topic: E-poster
Keyword(s): Immune response, T regulatory cells, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Programmed death-1 (PD-1) receptor and its ligands (PD-L1 and PD-L2) are involved in attenuating tumor immunity and facilitating tumor progression. PD-1, PD-L1 and PD-L2 therapeutic blocking agents have been reported to have significant antitumor effects. In chronic myeloid leukemia (CML), the expression of this receptor and its ligands is not fully characterized for the different subsets of cells of the immune system in which their expression is found constitutively or post-induction.
Aims
In this study, we analyzed the expression of PD-1 and its ligands on regulatory T cells (Tregs) in chronic phase CML patients to understand the mechanisms underlying suppressor effects that inhibit the anti-leukemia immune response.
Methods
Peripheral blood samples from chronic phase CML patients (n=50) under Interferon-alpha 2b (IFN-α 2b), imatinib, dasatinb, nilotinib, bosutinib and ponatinib therapy were analyzed by multi-parametric flow cytometry for the characterization of regulatory T cells and surface expression of PD-1. Buffy coats (n=13) from healthy blood donors were used as control. Cytokines and chemokines were evaluated in a 34-plex panel by xMAP technology (Luminex®). Gene expression analysis and miRNA profiling were also performed for these samples.
Results
PD-1 Tregs were found significantly decreased (p<0.0001) in CML patients and down-regulation of this receptor was also observed (p<0.01). Naïve and memory Treg subsets were equally affected. No significant alterations were observed for PD-L1 and PD-L2 ligands. Although TGF-β and IL-10 production were not significantly altered by down-regulation of PD-1 in Tregs, the overall effect of tyrosine kinase inhibitor (TKI) therapy suggests a negative impact in these cells concerning the anti-leukemic immune response.
Conclusion
Regulatory T cells represent a major population of suppressors in the immune response against leukemia. Down-regulation of PD-1 receptor in Tregs during chronic phase CML reinforces the notion that discontinuation of treatment must be carefully evaluated beforehand, since these suppressor cells could permit the proliferation of existent residual leukemic cells.
Session topic: E-poster
Keyword(s): Immune response, T regulatory cells, Tyrosine kinase inhibitor
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