Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Cancer Immunol Immunother. 2019 Aug;68(8):1341-1350. doi: 10.1007/s00262-019-02366-0. Epub 2019 Jul 19.
Gastric cancer (GC) is the most common malignant tumor in digestive organs, and the prognosis of GC patients who have undergone surgery remains poor because of frequent recurrence. Therefore, the identification of new markers to predict the outcome of these patients is needed. Monocyte count is a negative prognostic factor associated with inflammation. We investigated the relationship between peripheral monocytes in the peri-operative period and prognosis in GC patients. A high pre-operative monocyte count was identified as a prognostic factor in a retrospective analysis of 278 stage II and III GC patients who underwent curative gastrectomy. In contrast, an increased post-operative monocyte count compared to the pre-operative monocyte count was a marker of poor prognosis, particularly for early relapse. In a prospective analysis of 75 GC patients, a subset of the increased post-operative monocytes was similar to CD14 HLA-DR CD11b CD33 cells by flow cytometry, and these monocytes produced IDO and arginase and suppressed T cell functions; therefore, we classified these cells as monocytic myeloid-derived suppressive cells (M-MDSCs). Peri-operative neutrophils and C-reactive protein (CRP), which are also related to inflammation, did not affect the prognosis of GC patients, and a neutrophil immunosuppressive function was not observed. These results suggest that peripheral monocytes in the peri-operative period in GC patients are a useful marker for the prognosis of GC patients, and a subset of increased post-operative monocytes may be characterized as M-MDSCs.
胃癌(GC)是最常见的消化系统恶性肿瘤,由于术后经常复发,GC 患者的预后仍然较差。因此,需要识别新的标志物来预测这些患者的结局。单核细胞计数是与炎症相关的负性预后因素。我们研究了围手术期外周血单核细胞与 GC 患者预后的关系。在对 278 例接受根治性胃切除术的 II 期和 III 期 GC 患者的回顾性分析中,术前高单核细胞计数被确定为预后因素。相比之下,与术前单核细胞计数相比,术后单核细胞计数增加是预后不良的标志物,尤其是早期复发。在对 75 例 GC 患者的前瞻性分析中,通过流式细胞术,术后增加的单核细胞亚群与 CD14 HLA-DR CD11b CD33 细胞相似,这些单核细胞产生 IDO 和精氨酸酶并抑制 T 细胞功能;因此,我们将这些细胞归类为单核细胞髓系来源的抑制细胞(M-MDSCs)。围手术期中性粒细胞和 C 反应蛋白(CRP),也与炎症有关,并不影响 GC 患者的预后,也没有观察到中性粒细胞的免疫抑制功能。这些结果表明,GC 患者围手术期外周血单核细胞是 GC 患者预后的有用标志物,术后增加的单核细胞亚群可能具有 MDSC 特征。