Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia
Open Access
- 31 January 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (1), e55818
- https://doi.org/10.1371/journal.pone.0055818
Abstract
Immunotherapy (eg interferon α) in combination with tyrosine kinase inhibitors is currently in clinical trials for treatment of chronic myeloid leukemia (CML). Cancer patients commonly have problems with so called immune escape mechanisms that may hamper immunotherapy. Hence, to study the function of the immune system in CML is of interest. In the present paper we have identified immune escape mechanisms in CML with focus on those that directly hamper T cells since these cells are important to control tumor progression. CML patient samples were investigated for the presence of myeloid-derived suppressor cells (MDSCs), expression of programmed death receptor ligand 1/programmed death receptor 1 (PD-L1/PD-1), arginase 1 and soluble CD25. MDSC levels were increased in samples from Sokal high risk patients (p<0,05) and the cells were present on both CD34 negative and CD34 positive cell populations. Furthermore, expression of the MDSC-associated molecule arginase 1, known to inhibit T cells, was increased in the patients (p = 0,0079). Myeloid cells upregulated PD-L1 (p<0,05) and the receptor PD-1 was present on T cells. However, PD-L1 blockade did not increase T cell proliferation but upregulated IL-2 secretion. Finally, soluble CD25 was increased in high risk patients (p<0,0001). In conclusion T cells in CML patients may be under the control of different immune escape mechanisms that could hamper the use of immunotherapy in these patients. These escape mechanisms should be monitored in trials to understand their importance and how to overcome the immune suppression.Keywords
This publication has 56 references indexed in Scilit:
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerNew England Journal of Medicine, 2012
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerNew England Journal of Medicine, 2012
- Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13Cancer Immunology, Immunotherapy, 2011
- Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastomaNeuro-Oncology, 2011
- Overall survival and PD‐L1 expression in metastasized malignant melanomaCancer, 2010
- T regulatory cells control T‐cell proliferation partly by the release of soluble CD25 in patients with B‐cell malignanciesImmunology, 2010
- Anti-inflammatory Triterpenoid Blocks Immune Suppressive Function of MDSCs and Improves Immune Response in CancerClinical Cancer Research, 2010
- PD‐1 signaling in primary T cellsImmunological Reviews, 2009
- A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T CellsGastroenterology, 2008
- Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapyCancer Immunology, Immunotherapy, 2008