Instituto de Imunologia
Contributions
Type: Publication Only
Background
Different effects on the immune system are reported at the diagnosis and during therapy depending on Tyrosine Kinase Inhibitors (TKI) and interferon-alpha protocols. Some of these are dose-dependent effects. At present time, several clinical trials are establishing also the safety parameters for cessation of therapy in a selected group of Chronic Myeloid Leukemia (CML) patients. Although there is no consensus for laboratory evaluation of immune response for clinical trials, the Human Immunophenotyping Consortium (HIPC) aims at the standardization of protocols based on multicolor flow cytometry (Maecker et al. Nat Rev Immunol 2012).
Aims
The current study aimed at the evaluation of the immune status in treated CML patients to establish addtional efficacy parameters of different therapeutic strategies.
Methods
We used an extended 10-parameter panel for the analysis of T cells (Th1, Th2, Th17, Tregs), B cells (including plasmablasts), monocytes (classical and non-classical), dendritic cells (myeloid and plasmacytoid) and NK cells (CD56bright and CD56dim) in CML immune monitoring. Additionally, activation and maturation profile, as well as memory status was investigated for T and B cells. Intracellular cytokine staining, phosphorylation studies, response to multiple stimuli and gene expression profiling of relevant sorted cells was also performed for evaluation of immune response in these patients. Deep analysis of specific subsets (NK, NKT and γδ T cells) and pathways (CD137, PD-1, CD96, CD226, TIGIT) were explored.
Results
Significant impact on NK cells, NKT and Th17 cells was observed in CML patients undergoing therapy with TKI. Maturation and activation status of different lymphocyte subsets was found affected by therapy. Optimal response was found associated to immune response robustness of CML patients.
Summary
In conclusion, CML successful treatment is highly influenced by the immune response and an immune-based monitoring could be an important tool in the near future.
Financial Support: FEDER (Programa Operacional Factores de Competitividade – COMPETE) and FCT (Fundação para a Ciência e a Tecnologia) through project PEst-C/SAU/LA0001/2013-2014.
Keyword(s): Chronic myeloid leukemia, Immunity, Monitor, Tyrosine kinase inhibitor
Session topic: Publication Only
Type: Publication Only
Background
Different effects on the immune system are reported at the diagnosis and during therapy depending on Tyrosine Kinase Inhibitors (TKI) and interferon-alpha protocols. Some of these are dose-dependent effects. At present time, several clinical trials are establishing also the safety parameters for cessation of therapy in a selected group of Chronic Myeloid Leukemia (CML) patients. Although there is no consensus for laboratory evaluation of immune response for clinical trials, the Human Immunophenotyping Consortium (HIPC) aims at the standardization of protocols based on multicolor flow cytometry (Maecker et al. Nat Rev Immunol 2012).
Aims
The current study aimed at the evaluation of the immune status in treated CML patients to establish addtional efficacy parameters of different therapeutic strategies.
Methods
We used an extended 10-parameter panel for the analysis of T cells (Th1, Th2, Th17, Tregs), B cells (including plasmablasts), monocytes (classical and non-classical), dendritic cells (myeloid and plasmacytoid) and NK cells (CD56bright and CD56dim) in CML immune monitoring. Additionally, activation and maturation profile, as well as memory status was investigated for T and B cells. Intracellular cytokine staining, phosphorylation studies, response to multiple stimuli and gene expression profiling of relevant sorted cells was also performed for evaluation of immune response in these patients. Deep analysis of specific subsets (NK, NKT and γδ T cells) and pathways (CD137, PD-1, CD96, CD226, TIGIT) were explored.
Results
Significant impact on NK cells, NKT and Th17 cells was observed in CML patients undergoing therapy with TKI. Maturation and activation status of different lymphocyte subsets was found affected by therapy. Optimal response was found associated to immune response robustness of CML patients.
Summary
In conclusion, CML successful treatment is highly influenced by the immune response and an immune-based monitoring could be an important tool in the near future.
Financial Support: FEDER (Programa Operacional Factores de Competitividade – COMPETE) and FCT (Fundação para a Ciência e a Tecnologia) through project PEst-C/SAU/LA0001/2013-2014.
Keyword(s): Chronic myeloid leukemia, Immunity, Monitor, Tyrosine kinase inhibitor
Session topic: Publication Only