Significance of myeloid-derived suppressor cells (MDSCs) like CD14+B7-H4 cells frequency in blood and tumor microcirculation of lung cancer patients

Abstract

Background/Aim. Myeloid-derived suppressor cells (MDSCs) suppress immune responses via a series of inhibitory mechanisms, which ultimately could lead to tumor growth. B7-H4 expression is significantly associated with poor outcome and promotion of tumor cell proliferation, invasion and migration in patients with various cancers. Data concerning B7-H4 expression in lung cancers (LC), either on tumor or immunological cells, are still sporadic. The aim was to estimate and correlate the number of CD14+B7-H4+MDSCs in blood and lung tumor microcirculation with clinical stage, histology type of tumor, tumor node metastasis (TNM) stadium, nodal status and disease outspread. Methods. The study included 44 lung cancer patients (III and IV clinical stage) and 30 healthy controls. CD14+B7-H4+ MDSC number was estimated by flow cytometry in blood and tumor microcirculation samples of each patient. Results. CD14+B7-H4+ MDSCs number was significantly higher in patients’ samples compared to controls. CD14+B7-H4+ MDSC number was significantly increased in tumor compared to blood sample of the same patient. Clinical stage III patients had the increased number of the CD14+B7-H4+ MDSC compared to stage IV, in both types of samples. According to histology, small cell lung cancer (SCLC) patients had the highest average CD14+B7-H4+ MDSCs number, significantly increased compared to patients with squamous and large cell LC histology type. Tumor size was directly associated with the number of the CD14+B7-H4+ MDSC, both in blood and tumor samples. Furthermore, nodal involvement was associated with the gradual increase of the CD14+B7-H4+ MDSC number, being the highest in the N3 group, again both in blood and tumor samples. Finally, we detected higher CD14+B7-H4+ MDSCs number in the samples of patients without metastases. Conclusion. CD14+B7-H4+ MDSCs n umber in L C patients is significantly associated with tumor histology type, lymph node involvement, disease extent degree and tumor size. Concerning their large number in LC tumor microenvironment together with immunosuppressive capacities, CD14+B7-H4+ MDSCs could represent important tumor promoting factor in LC pathophysiology.

Keywords

• lung neoplasms
• myeloid-derived suppressor cells
• immunologic factors
• neoplasm metastasis
• flow cytometry
• histology