基底细胞型乳腺癌患者肿瘤内树突状细胞呈HLA-DR抗原表达细胞的临床意义

观察基底细胞型乳腺癌患者肿瘤内树突状细胞、呈HLA-DR抗原表达细胞引起的抗肿瘤免疫并探讨其临床意义。方法：应用免疫组织化学二步法检测基底细胞型乳腺癌患者肿瘤组织内S-100蛋白阳性的树突状细胞及呈HLA-DR抗原阳性表达的细胞。结果：基底细胞型乳腺癌患者肿瘤组织内缺乏树突状细胞（2/22,占9.09%）,数量明显少于非基底细胞型乳腺癌患者（138/138,占100%）,癌细胞的HLA-DR抗原阳性表达（4/22,占18.1%）明显少于非基底细胞型乳腺癌（106/138,占76.8%）。结论：基底细胞型乳腺癌患者肿瘤组织缺乏由树突状细胞、淋巴细胞及HLA-DR抗原阳性表达的癌细胞引起的特异性抗肿瘤免疫,这与基底细胞型乳腺癌患者预后差可能密切相关。     

Kynurenine pathway alteration in acute pancreatitis and its role as a biomarker of infected necrosis

IntroductionInfected pancreatic necrosis (IPN) is a major cause of mortality in acute pancreatitis (AP). Currently, no specific strategies are available to predict the development of IPN. Earlier we reported that persistent down-regulation of HLA-DR increases risk of developing IPN. Altered kynurenine pathway (KP) metabolites showed poor prognosis in sepsis. Here we evaluated the role of HLA-DR and KP in IPN.MethodsPatients with ANP and healthy controls were enrolled. Demographic and clinical parameters were recorded. Circulating interleukin (IL)-8, 6, 1β, 10, Tumor necrosis factor-α were quantified using flowcytometry. Plasma procalcitonin, endotoxin, and KP (tryptophan, kynurenine) concentrations were estimated using ELISA. qRT-PCR was conducted to evaluate mRNA expression of HLA-DR, IL-10, Toll like receptor-4 (TLR-4), and kynurenine-3-monooxygenase (KMO) genes on peripheral blood mononuclear cells. Plasma metabolites were quantified using gas chromatography mass spectrometry (GC-MS/MS). Standard statistical methods were used to compare study groups. Metaboanalyst was used to analyse/visualize the metabolomics data.ResultsWe recruited 56 patients in Cohort-1 (IPN:26,Non-IPN:30), 78 in Cohort-2 (IPN:57,Non-IPN:21), 26 healthy controls. Increased cytokines, endotoxin, and procalcitonin were observed in patients with IPN compared to Non-IPN. HLA-DR and KMO gene expressions were significantly down-regulated in IPN groups, showed positive correlation with one another but negatively correlated with IL-6 and endotoxin concentrations. Increased IDO and decreased plasma tryptophan were observed in IPN patients. Metabolome analysis showed significant reduction in several essential amino acids including tryptophan in IPN patients. Tryptophan, at a concentration of 9 mg/ml showed an AUC of 91.9 (95%CI 86.5–97.4) in discriminating IPN.ConclusionHLA-DR downregulation and KP alteration are related to IPN. The KP metabolite plasma tryptophan can act as a potential biomarker for IPN.