Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Am J Reprod Immunol. 2021 Mar;85(3):e13343. doi: 10.1111/aji.13343. Epub 2020 Sep 21.
Previous studies identified circulating CD14 HLA-DR monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre- and post-frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy.
Incident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33 CD11b HLA-DR CD14 CD15 monocytic cells, henceforth termed CD14 HLA-DR monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14 HLA-DR monocytic cell percentages and disease stage. Wilcoxon signed-rank tests evaluated changes in these monocytic cell levels pre- and post-chemotherapy in a patient subset (n = 70).
Patients with elevated frequencies of circulating CD14 HLA-DR monocytic cells at diagnosis were at 3.33-fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04-10.64), with a significant trend in increasing CD14 HLA-DR monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post-chemotherapy among a subset of patients with advanced stage disease (P < .0001).
These findings support the potential clinical relevance of CD14 HLA-DR monocytic cells in EOC for prognosis and may indicate a non-invasive biomarker to measure disease progression.
先前的研究表明，循环 CD14 HLA-DR 单核细胞作为一种免疫抑制亚群存在于实体恶性肿瘤中，如前列腺癌、肾细胞癌和胰腺癌。这些单核细胞不仅与肿瘤进展有关，而且可能成为免疫治疗的潜在障碍。本研究检查了循环单核细胞的频率与上皮性卵巢癌（EOC）进展之间的关系，这种进展以前线化疗前和后的疾病阶段来定义，这是该恶性肿瘤的一个主要预后因素。
招募了 236 名患有 EOC 的女性新发病例，并利用综合流式细胞术评估了外周血 CD33 CD11b HLA-DR CD14 CD15 单核细胞（以下简称 CD14 HLA-DR 单核细胞）的频率，然后在完成一线化疗之前和之后进行评估。多变量比值比（OR）用于估计 CD14 HLA-DR 单核细胞百分比与疾病阶段之间的关联。Wilcoxon 符号秩检验评估了患者亚组（n=70）化疗前后这些单核细胞水平的变化。
在诊断时循环 CD14 HLA-DR 单核细胞频率升高的患者患有晚期（III/IV 期）EOC 的可能性高出 3.33 倍（CI：1.04-10.64），并且 CD14 HLA-DR 单核细胞水平呈上升趋势（P=0.04）。在患有晚期疾病的患者亚组中，这些单核细胞的中位数下降了 2.02%（P<.0001）。
这些发现支持 CD14 HLA-DR 单核细胞在 EOC 中用于预后的潜在临床相关性，并且可能表明可以测量疾病进展的非侵入性生物标志物。
