Background: Ovarian cancer ascites contributes to the immunosuppressive tumor microenvironment (TME) via macrophage-derived chemokine ligand 23 (CCL23) signaling, T-cell exhaustion, and upregulating pro-inflammatory cytokines. However, the extent to which ascites-derived CCL23 concentrations associate with changes in pro- and anti-inflammatory cytokines and overall patient survival in ovarian cancer patients remains unknown.Methods: CCL23 concentrations and pro-inflammatory cytokines were measured from ascites of stage III and IV epithelial ovarian cancer patients by ELISA and Luminex assays, respectively. Kaplan–Meier survival analysis was performed using patient outcome data from Stanford University Hospital and the Cancer Genome Atlas. The impact of CCL23 peptides on pro-inflammatory cytokine secretion was evaluated in vitro using differentiated THP-1 monocytes.Results: A total of 40 patients were enrolled and CCL23 concentrations were detected in all ascites samples (median = 2.42 ng/mL; range [0.06–6.45]). Reduced survival time corresponded with high CCL23 containing samples (mOS: 3.2 years, [3.9 ng/mL]) versus intermediate (mOS: 6.0 years, [2.5 ng/mL]) or low (mOS: 5.9 years; [1.4 ng/mL]) groups. TGCA analysis of patient outcomes was confirmatory. A significant negative correlation was observed between high CCL23 ascites concentrations versus CXCL10 and soluble PD-1 cytokine levels. High tumor expression of CXCL10 was associated with improved survival (mOS; 5.9 years) versus low CXCL10 expression (mOS; 3.2 years). In vitro, CCL23-stimulated THP-1 macrophages exhibited reduced CXCL10 secretion via STAT-3 activation.Conclusions: High CCL23 concentrations in ovarian cancer ascites reduces CXCL10 secretion from myeloid cells and associates with reduced patient survival.
背景：卵巢癌腹水通过巨噬细胞源性趋化因子配体23（CCL23）信号传导、T细胞耗竭及促炎细胞因子上调，促进免疫抑制性肿瘤微环境（TME）的形成。然而，腹水来源的CCL23浓度与卵巢癌患者促炎/抗炎细胞因子变化及总体生存期的关联程度尚未明确。 方法：分别采用ELISA和Luminex检测技术，对III-IV期上皮性卵巢癌患者腹水中的CCL23浓度及促炎细胞因子进行定量分析。基于斯坦福大学医院及癌症基因组图谱（TCGA）的患者预后数据开展Kaplan-Meier生存分析。通过体外实验评估CCL23多肽对分化THP-1单核细胞促炎细胞因子分泌的影响。 结果：共纳入40例患者，所有腹水样本均检出CCL23（中位浓度=2.42 ng/mL；范围[0.06–6.45]）。高CCL23浓度组（中位浓度3.9 ng/mL）患者中位总生存期（3.2年）显著低于中浓度组（2.5 ng/mL，6.0年）与低浓度组（1.4 ng/mL，5.9年）。TCGA数据库分析结果与此吻合。高CCL23腹水浓度与CXCL10及可溶性PD-1细胞因子水平呈显著负相关。肿瘤组织高表达CXCL10患者中位生存期（5.9年）优于低表达组（3.2年）。体外实验证实CCL23通过激活STAT-3信号通路抑制THP-1巨噬细胞的CXCL10分泌。 结论：卵巢癌腹水中高浓度CCL23可通过抑制髓系细胞CXCL10分泌，进而导致患者生存期缩短。
肿瘤(癌症)患者之家