title: Arginase-1 mRNA expression correlates with myeloid-derived suppressor cell levels in peripheral blood of NSCLC patients.
abstract: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with immunosuppressive activity that are increased in cancer patients. Until now, the characterization of MDSC in humans was very challenging. The aim of this study was to determine the characterization and optimal assessment of MDSC and to investigate their presence and function in blood of advanced-stage NSCLC patients. We determined MDSC and lymphocyte populations in peripheral blood mononuclear cells (PBMC) samples of 185 treatment-naïve NSCLC patients and 20 healthy controls (HC). NSCLC patients had an increased population of PMN-MDSC compared to HC (p < 0.0001). Frequencies of CD4(+) and CD8(+) T-cells were significantly decreased in NSCLC patients (p < 0.0001 and p = 0.05). We found that PMN-MDSC were able to suppress T-cell proliferation in vitro. qRT-PCR showed that arginase-1 (Arg-1) mRNA is mainly expressed by MDSC and that the level of Arg-1 in PBMC correlates with the frequency of MDSC in PBMC (Spearman's rho: 0.797). There were significant differences in MDSC and lymphocyte populations between NSCLC patients and HC. We found that MDSC frequencies are stable up to six hours at room temperature after blood was drawn and that cryopreservation leads to a strong decrease of MDSC in PBMC. We show that Arg-1 mRNA expression is a valuable method to determine the levels of MDSC in peripheral blood of cancer patients. This method is therefore a useful alternative for the complex flowcytometric analysis in large multicenter patient studies.
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands. Electronic address: m.heuvers@erasmusmc.nl.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Heuvers
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Muskens
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Bezemer
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands.
authors.forename: Margaretha
authors.initials: M
authors.lastname: Lambers
authors.affiliation: Department of Pulmonary Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Anne-Marie C
authors.initials: AC
authors.lastname: Dingemans
authors.affiliation: Department of Pulmonary Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry J M
authors.initials: HJM
authors.lastname: Groen
authors.affiliation: Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands.
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands.
authors.forename: Joost P J J
authors.initials: JPJJ
authors.lastname: Hegmans
authors.affiliation: Department of Pulmonary Medicine, Erasmus Medical University Center, Rotterdam, The Netherlands; Department of Pulmonary Medicine, Amphia Hospital Breda, The Netherlands.
authors.forename: Joachim G J V
authors.initials: JGJV
authors.lastname: Aerts
mesh_terms: D000368:Aged; D001119:Arginase / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015925:Cryopreservation; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009367:Neoplasm Staging; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C574619:ARG1 protein, human; D001119:Arginase
keywords: Arginase-1; Immuno-oncology; Myeloid-derived suppressor cells; NSCLC