The Promoting Angiogenesis and Its Clinical Significance of CD33 + Myeloid Derived Suppressor Cells Derived From Small Cell Lung Cancer

ABSTRACT Background Myeloid‐derived suppressor cells (MDSCs) are important tumor microenvironment components in small cell lung cancer (SCLC). We successfully identified MDSCs expressing the surface marker CD33 in SCLC; nonetheless, whether CD33 + MDSCs promote SCLC angiogenesis remains unclear. This study aims to explore the angiogenic effect and clinical significance of CD33 + MDSCs derived from SCLC. Method Nineteen patients diagnosed with extensive‐stage SCLC at Jilin Cancer Hospital were selected as the research subjects. CD33 + MDSCs were isolated from the peripheral blood of patients with SCLC using magnetic bead separation and CD33 expression was detected by flow cytometry. The angiogenic potential of CD33 + MDSCs derived from the peripheral blood of patients with SCLC and healthy individuals was assessed using human umbilical vein endothelial cell (HUVEC) angiogenesis assays, and the clinical significance of CD33 + MDSCs in promoting angiogenesis in patients with SCLC was analyzed using clinical data. Results Compared to healthy individuals, the CD33 + MDSCs (CD14 + CD33 + ) isolated from the peripheral blood of SCLC patients exhibited a greater ability to promote HUVEC tubular growth (average vessel length: 57.60 mm [47.78 mm] vs. 39.07 mm [15.84 mm], p = 0.000; vessel area: 371,890 mm³ [699,927 mm³] vs. 334,652 mm³ [219,520 mm³], p < 0.000; total number of junctions: 141 [301] vs. 120 [94], p < 0.005), and their angiogenic ability was associated with older age, female sex, high performance status scores, no systematic treatment, and treatment unresponsiveness ( p < 0.050). Furthermore, the enhanced angiogenic ability of CD33 + MDSCs may represent a risk factor for treatment unresponsiveness (average vessel length: Odds ratio = 3.904, 95%CI = 1.812–8.409, p = 0.001; vessel area: Odds ratio = 2.501, 95%CI = 1.187–5.267, p = 0.016; total number of junctions: Odds ratio = 3.630, 95%CI = 1.686–7.815, p = 0.001) and is associated with a poor SCLC prognosis (average vessel length: Hazard ratio = 2.210, 95% CI = 1.299–3.758, p = 0.003; vessel area: Hazard ratio = 2.170, 95% CI = 1.274–3.693, p = 0.004; total number of junctions: Hazard ratio = 2.267, 95% CI = 1.333–3.853, p = 0.003). Conclusion CD33 + MDSCs derived from the peripheral blood of patients with SCLC promote angiogenesis, which is a risk factor for treatment unresponsiveness and is associated with poor prognosis.