Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease

Abstract

Elevated levels of myeloid-derived suppressor cells (MDSCs) induced by tumor-derived factors are associated with inhibition of immune responses in patients with gastrointestinal malignancies. We hypothesized that pro-MDSC cytokines and levels of MDSC in the peripheral blood would be elevated in pancreatic adenocarcinoma patients with progressive disease. Peripheral blood mononuclear cells (PBMCs) were isolated from 16 pancreatic cancer patients undergoing chemotherapy and phenotyped for MDSC using a five antigen panel (CD33, HLA-DR, CD11b, CD14, CD15). Patients with stable disease had significantly lower MDSC levels in the peripheral blood than those with progressive disease (1.41 ± 1.12 vs. 5.14 ± 4.58 %, p = 0.013, Wilcoxon test). A cutoff of 2.5 % MDSC identified patients with progressive disease. Patients with ECOG performance status ≥2 had a weaker association with increased levels of MDSC. Plasma was obtained from 15 chemonaive patients, 13 patients undergoing chemotherapy and 9 normal donors. Increases in the levels of pro-MDSC cytokines were observed for pancreatic cancer patients versus controls, and the pro-MDSC cytokine IL-6 was increased in those patients undergoing chemotherapy. This study suggests that MDSC in peripheral blood may be a predictive biomarker of chemotherapy failure in pancreatic cancer patients.

Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent

“…Consistent with the present findings, many previous studies investigating similar human MDSC phenotypes in other cancer types have demonstrated a correlation between higher MDSC levels and more advanced clinical stage (30,40,41), metastatic burden (41,42), disease progression (41,42,43), and worse patient survival (28,29,44,45). The current data further confirm the role of circulating MDSC as a tool for disease detection and monitoring across cancer types.…”

Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer

“…The existence of multiple classes of immune suppressor cells, their presence in high numbers in most tumor types, and their requirement for tumor growth in animal models underscores their importance to tumor development. Consequently, suppressor immune cell levels may predict tumor burden, prognosis and response to therapy [6]. Furthermore, in the last decade, pre-clinical research demonstrated that certain chemotherapeutic agents such as platinum compounds, anti-metabolites and taxanes can modulate the levels and function of these suppressive immune cell subsets and by doing so can affect tumor growth indirectly [7–10].…”

Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages

“…In fact, survival estimates for patients with high numbers of immature MDSCs (lineage -HLA-DR lo/-CD11b + CD33 + ) in the blood prior to starting standard chemotherapy were associated with shorter overall survival (OS) (133). Finally, high levels of MDSCs, cytokines, and chemo kines (PDGF, IL-4, IL-8, IL-17, FGF-2, CCL5, and VEGF) in patients with PDAC are associated with progressive disease (134).…”