Correlation Of Circulating Tumor Cells With Myeloid-Derived Suppressive Cells In The Peripheral Blood Of Patients With Advanced Small Cell Lung Cancer

The accumulation of Myeloid-derived Suppressor Cells (MDSCs) and the Circulating Tumor Cells (CTCs) have been proposed as negative prognostic biomarkers in several tumors, including SCLC. However, no studies have shown a correlation of the MDSCs with CTCs in SCLC patients. We aimed to investigate the clinical relevance of CTCs and MDSCs in progressing patients with advanced SCLC. Peripheral blood was obtained from 32 SCLC patients at the time of progression after 1st line chemotherapy and 31 healthy controls (HC). Immune cells were determined using flow cytometry and CTCs were detected using both the CellSearch System (CS) and immunofluorescence double staining of PBMCs with anti-TTF1 and/or anti-CD56 and anti-CD45 antibodies (IF). The median percentage of patients MDSCs at baseline was used to characterize MDSCs as high or low. For the CTCs detection using the CS and IF, the cut-off values were ≥5 and ≥1 CTCs, respectively. The percentage of naïve CD4+ T cells was decreased in patients vs NC at baseline. The whole population of MDSCs (CD33+Lin-HLA-DR-/low), as well as the granulocytic (G)-(CD15+CD14-CD33+CD11b+) and the monocytic (M)-MDSCs (CD14+CD15+CD33+CD11b+Lin-HLA-DR-/low) were significantly increased in patients (p < 0.0001). Only M-MDSCs levels were significantly correlated with TTF1+ (p <0.018) but not with CD56+ or TTF1+/CD56+ CTCs. Conversely, there was no correlation of the different MDSCs subtypes with the CTCs detected using the CS. Patients with high M-MDSCs levels had a higher absolute number of TTF-1+ CTCs compared to patients with low M-MDSC levels (Mean: 46 vs 2 cells; p = 0.02) whereas the frequency of M-MDSCs was higher in patients with TTF-1+ CTCs compared to those with TTF-1- CTCs (mean: 4.6% vs 1.7%; p = 0.01). We showed an increased frequency of M-MDSCs in the blood of patients with SCLC at relapse exhibiting a positive correlation with CTCs. These observations seem to indicate that some CTCs' subpopulations may be escape and proliferate in patients with active immunosuppressive mechanisms.