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.