ABSTRACT
Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.
ABSTRACT
Bullous pemphigoid (BP) is a chronic debilitating autoimmune blistering disease that frequently occurs in the elderly population. Previous studies have suggested a high morbidity and mortality associated with BP. However, relatively few studies have investigated prognostic factors of BP mortality, and they showed considerably various results. This meta-analysis aimed to quantitatively assess the association between several potential prognostic factors and risk of mortality in bullous pemphigoid. A comprehensive search was performed using Pubmed, Embase, and Cochrane Library. Cohort studies that assessed prognostic factors of BP mortality were included. Random-effects model was utilized to calculate the pooled hazard ratio (HR). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Egger's test. 14 studies were included comprising 2499 patients. Combined HRs suggested that advanced age (HR 1.63, 95% CI 1.34-1.97), presence of circulating antibodies (HR 1.77, 95% CI 1.20-2.62), concomitant dementia (HR 2.01, 95% CI 1.22-3.33), and concomitant stroke (HR 1.86, 95% CI 1.29-2.67) have an unfavorable impact on patient survival. Gender, disease extent, mucosal involvement, and indirect immunofluorescence result were not shown to be linked to mortality by our analysis. This study indicated that BP patients with older age, circulating antibodies, dementia, and stroke are at greater risk of mortality. Clinicians should be aware of this association and utilize this information in patient education and treatment process.
