Clinical relevance of systemic monocytic-MDSCs in patients with metastatic breast cancer

Abstract

The overall aim of this prospective study was to delineate the role of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in patients with metastatic breast cancer (MBC). MDSCs are a heterogeneous group of immunosuppressive cells often enriched in different malignancies which hold prognostic and predictive value for clinical outcomes. Here, we assessed the clinical significance of Mo-MDSCs in 54 patients with de novo or distant recurrent MBC. We show that high levels of Mo-MDSCs significantly correlated with de novo MBC (metastatic disease at initial diagnosis), estrogen receptor (ER) negativity, and liver- and bone metastasis. A trend towards an association between high levels of Mo-MDSCs and survival (P = 0.053) was also found in patients with distant recurrent ER-positive MBC. We therefore propose that an increased population of Mo-MDSCs may be related to the metastatic or immunoregulatory switch associated with transition to a more systemic disease. Our data imply that high levels of systemic Mo-MDSCs represent patients with more aggressive disease and worse outcome.

Keywords: Breast cancer; Estrogen receptor; Metastasis; Mo-MDSCs; Survival.

Fig. 1

Mo-MDSCs are enriched in the peripheral blood of MBC patients. Peripheral blood was collected from 54 patients with metastatic breast cancer (MBC) and 22 healthy controls (HC). Percentage of CD14⁺HLA-DR^low/− Mo-MDSCs was assessed by flow cytometry. a Median percentage of Mo-MDSC in HC and MBC patients with normal (n = 28) and high (n = 26) levels of Mo-MDSCs. Cut-off level between normal and high levels of Mo-MDSCs was set to the highest value of Mo-MDSCs in HCs (8.29% of PBMCs), as described in [28]. Error bars; SEM. Exact P values, by Kruskal Wallis with Dunn’s multiple comparison test, are indicated. b Receiver operating characteristic (ROC) curve of percentage Mo-MDSCs in healthy controls (HC, n = 22) and MBC patients (n = 54). Area under the curve (AUC) and significance are indicated

Fig. 2

Percentages of Mo-MDSCs in patients divided by clinicopathological features. CD14⁺HLA-DR^low/− Mo-MDSCs in peripheral blood was assessed by flow cytometry and stratified according to clinicopathological features (see Table 1). Median percentage of Mo-MDSCs as divided by (a) metastatic site or (b) according to de novo or distant recurrent MBC. Error bars; SEM. Exact P values, by Mann–Whitney Wilcoxon, are indicated

Fig. 3

Mo-MDSC levels and associations with survival. Kaplan–Meier curves of progression-free survival (PFS) and overall survival (OS) according to Mo-MDSC levels in all MBC patients (n = 54, a–b) or in MBC patients with distant recurrence (n = 42, c–d). Statistics by Log-rank test

Fig. 4

Mo-MDSC levels and associations with survival in distant recurrent MBC patients stratified for tumor ER status. Kaplan–Meier curves of progression-free survival (PFS) and overall survival (OS) in relation to Mo-MDSC levels in MBC patients with ER-positive primary tumors (n = 30, a–b) or in MBC patients with ER-negative primary tumors (n = 8, c–d). Statistics by Log-rank test