Vol 49, No 1 (2011)
Original paper
Submitted: 2011-12-19
Published online: 2011-04-19
Evaluation of monocyte-derived dendritic cells, T regulatory and Th17 cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors
Iwona Hus, Jacek Tabarkiewicz, Magdalena Lewandowska, Magdalena Wasiak, Paulina Wdowiak, Maria Kusz, Monika Legieć, Anna Dmoszyńska, Jacek Roliński
DOI: 10.5603/FHC.2011.0022
·
Folia Histochem Cytobiol 2011;49(1):153-160.
Vol 49, No 1 (2011)
ORIGINAL PAPERS
Submitted: 2011-12-19
Published online: 2011-04-19
Abstract
Immunotherapy with dendritic cells (DC) may constitute a new and advantageous option for patients
with chronic myeloid leukemia (CML) who respond to therapy with tyrosine kinase inhibitors (TKI),
but do not reach complete cytogenetic or molecular remission. In this study, we evaluated the immunophenotype
of DC generated from monocytes (Mo-DC) of patients with CML and the influence of TKI therapy on
the results of CML-DC generation. We also measured the percentages of T regulatory cells (Tregs) as well as
Th17 cells in 19 untreated patients suffering from CML, and in 28 CML patients treated with TKI. We found
that DC can be reliably generated from the peripheral blood CD14+ cells of untreated CML patients. But we
observed a persistent expression of CD14 monocyte marker on DC from CML patients, together with lower
percentages of Mo-DC with expression of CD1a (p = 0.002), CD80 (p = 0.0005), CD83 (p = 0.0004), and
CD209 (p = 0.02) compared to healthy donors. There was an adverse correlation between WBC count and the
percentage of Mo-DC with co-expression of CD80 and CD86 (R = –0.63; p = 0.03). In patients treated with
TKI, we observed higher efficacy of DC generation in seven-day cultures, compared to untreated patients.
Expression of CD209 on DC was higher in patients treated with TKI (0.02). The duration of TKI therapy
correlated adversely with MFI for CD1a (R = –0.49; p = 0.006) and positively with MFI for CD83 (R = 0.63;
p = 0.01). Percentages of CD4+CD25highFoxP3+ cells (p = 0.0002) and Th17 cells (p = 0.02) were significantly
higher in untreated CML patients compared to healthy controls. There was a significant correlation between
the percentage of Treg cells and the percentage of peripheral blood basophiles (R = 0.821; p = 0.02). There
were no changes in Tregs or Th17 cell percentages in CML patients after six months of TKI therapy. However,
the expression of intracellular IL-17 in Th17 cells correlated negatively with the time of TKI therapy in the
whole group of treated patients (R = –0.516; p = 0.04). We noted a correlation between IL-6 serum level and
peripheral blood WBC count (R = 0.492; p = 0.04). There was also an inverse correlation between the serum
level of IL-6 and the duration of TKI therapy (R = –0.66; p = 0.03). Taken together, our data shows that
mature DC can be generated from CML patients treated with TKI, and that the yield of Mo-DC is higher in
patients treated with TKI than in patients with active disease. This should encourage further trials with DC
immunotherapy in patients with cytogenetic response after TKI therapy. We also found increased frequencies
of T regulatory and Th17 cells in CML patients, which might suggest their potential role in immunity against this disease. Further studies are needed to determine if manipulation of these cell populations might improve
the results of DC immunotherapy. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 153–160)
Abstract
Immunotherapy with dendritic cells (DC) may constitute a new and advantageous option for patients
with chronic myeloid leukemia (CML) who respond to therapy with tyrosine kinase inhibitors (TKI),
but do not reach complete cytogenetic or molecular remission. In this study, we evaluated the immunophenotype
of DC generated from monocytes (Mo-DC) of patients with CML and the influence of TKI therapy on
the results of CML-DC generation. We also measured the percentages of T regulatory cells (Tregs) as well as
Th17 cells in 19 untreated patients suffering from CML, and in 28 CML patients treated with TKI. We found
that DC can be reliably generated from the peripheral blood CD14+ cells of untreated CML patients. But we
observed a persistent expression of CD14 monocyte marker on DC from CML patients, together with lower
percentages of Mo-DC with expression of CD1a (p = 0.002), CD80 (p = 0.0005), CD83 (p = 0.0004), and
CD209 (p = 0.02) compared to healthy donors. There was an adverse correlation between WBC count and the
percentage of Mo-DC with co-expression of CD80 and CD86 (R = –0.63; p = 0.03). In patients treated with
TKI, we observed higher efficacy of DC generation in seven-day cultures, compared to untreated patients.
Expression of CD209 on DC was higher in patients treated with TKI (0.02). The duration of TKI therapy
correlated adversely with MFI for CD1a (R = –0.49; p = 0.006) and positively with MFI for CD83 (R = 0.63;
p = 0.01). Percentages of CD4+CD25highFoxP3+ cells (p = 0.0002) and Th17 cells (p = 0.02) were significantly
higher in untreated CML patients compared to healthy controls. There was a significant correlation between
the percentage of Treg cells and the percentage of peripheral blood basophiles (R = 0.821; p = 0.02). There
were no changes in Tregs or Th17 cell percentages in CML patients after six months of TKI therapy. However,
the expression of intracellular IL-17 in Th17 cells correlated negatively with the time of TKI therapy in the
whole group of treated patients (R = –0.516; p = 0.04). We noted a correlation between IL-6 serum level and
peripheral blood WBC count (R = 0.492; p = 0.04). There was also an inverse correlation between the serum
level of IL-6 and the duration of TKI therapy (R = –0.66; p = 0.03). Taken together, our data shows that
mature DC can be generated from CML patients treated with TKI, and that the yield of Mo-DC is higher in
patients treated with TKI than in patients with active disease. This should encourage further trials with DC
immunotherapy in patients with cytogenetic response after TKI therapy. We also found increased frequencies
of T regulatory and Th17 cells in CML patients, which might suggest their potential role in immunity against this disease. Further studies are needed to determine if manipulation of these cell populations might improve
the results of DC immunotherapy. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 153–160)
Keywords
chronic myeloid leukemia; tyrosine kinase inhibitors; dendric cells; T regulatory cells; Th17 cells
Title
Evaluation of monocyte-derived dendritic cells, T regulatory and Th17 cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors
Journal
Folia Histochemica et Cytobiologica
Issue
Vol 49, No 1 (2011)
Article type
Original paper
Pages
153-160
Published online
2011-04-19
Page views
2653
Article views/downloads
2075
DOI
10.5603/FHC.2011.0022
Bibliographic record
Folia Histochem Cytobiol 2011;49(1):153-160.
Keywords
chronic myeloid leukemia
tyrosine kinase inhibitors
dendric cells
T regulatory cells
Th17 cells
Authors
Iwona Hus
Jacek Tabarkiewicz
Magdalena Lewandowska
Magdalena Wasiak
Paulina Wdowiak
Maria Kusz
Monika Legieć
Anna Dmoszyńska
Jacek Roliński