Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer

Abstract

Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3, CD3CD4 and CD3CD8), neutrophils (CD66b) and polymorphonuclear-MDSC (PMN-MDSC; CD66bCD11bCD15CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3, CD3CD4 and CD3CD8 cells. PMN-MDSC% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3-739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0-18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.

Making cold malignant pleural effusions hot: driving novel immunotherapies

“…[101][102][103] Neutrophils and circulating neutrophil microRNAs serve as biomarkers for detection of NLSLC and are an independent negative predictor of survival in patients with advanced disease. [104][105][106] Mechanistic studies on the role of neutrophils in MPE are warranted given their immunosuppressive role in NSCLC and adverse prognostic value in MPE. 107 Dendritic cells (DCs) are professional antigen presenting cells (APCs) that cross-present antigens, induce adaptive immune responses, and regulate the immune system by modulating T and B lymphocyte antigen specific responses via their major histocompatibility (MHC) class I and II receptors and ability to produce IL-12 family cytokines.…”

Myeloid‑derived suppressor cells infiltration in non‑small‑cell lung cancer tumor and MAGE‑A4 and NY‑ESO‑1 expression

“…Furthermore, MDSCs can contribute to patient resistance to immunotherapy (22,23). Several studies have examined the association between the MAGE-A4 and NY-ESO-1 expression levels and survival (18,(24)(25)(26)(27)(28)(29), as well as the association between the MDSCs infiltrated in the tumor microenvironment and the survival of patients with different types of lung cancer (30)(31)(32)(33). However, the prognosis of the association between the MAGE-A4 or NY-ESO-1 and MDSCs has yet to be confirmed.…”

Myeloid derived suppressor cells contribute to the malignant progression of oral squamous cell carcinoma

“…Early evidence supported that MDSCs level was associated with clinical stage and distant metastasis in many human cancers including HNSCC, and surgical excision of tumors could decrease the concentration of peripheral blood MDSCs [27][28][29][30]29]. Hence, we addressed the number of infiltrated MDSCs by IHC in OSCC tissues and found that MDSCs were increased significantly in tumor stroma that was near to OSCC cells.…”