首页期刊导航|Journal of immunology research.
期刊信息/Journal information
Journal of immunology research.
Hindawi Publishing Corporation,
Journal of immunology research.

Hindawi Publishing Corporation,

2314-8861

Journal of immunology research./Journal Journal of immunology research.
正式出版
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    Neutrophil-to-Lymphocyte Ratio (NLR) Predicts PD-1 Inhibitor Survival in Patients with Metastatic Gastric Cancer

    Miaomiao GouTongtong QuZhikuan WangHuan Yan...
    1页
    查看更多>>摘要：Background and Aims. Biomarkers for systemic inflammation have been introduced into clinical practice for risk-rating in cancer patients' treatment. This study is aimed at confirming the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) as an effective biomarker for patients with metastatic gastric cancer (MGC) receiving anti-PD-1 agents. Method. Patients with MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The study analyzed the association of NLR and overall survival (OS) or progression-free survival (PFS) and antitumor response rate with PD-1 inhibitors. Results. 137 patients were included in the final analysis. The area under the curve value of NLR for 6-month OS was 0.71. The best cut-off value for NLR was 3.23. NLR < 3.23 was associated with longer OS (HR = 0.38, 95% CI, 0.26-0.57, p< 0.001) and PFS (HR = 0.42, 95% CI, 0.29-0.62, p< 0.001) in patients with MGC. No significant difference was observed in the objective response rate (ORR) (35.8% vs. 28.6%, p = 0.377) and disease control rate (DCR) (86.4% vs. 78.6%, p = 0.229) in the NLR < 3.23 group and in the NLR > 3.23 group, respectively. Univariate analysis and multivariate analysis found that NLR was an independent prognosis biomarker for PFS and OS. Conclusions. Pretreatment elevated NLR was significantly associated with inferior PFS and OS in patients with MGC who received anti-PD-1 inhibitors. Clinicians need to consider patients with elevated NLR for decisions on immunotherapy strategy.
      原文链接:
    • NSTL

    Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency

    Monica R. Meza-MezaJose Francisco Munoz-ValleAdolfo I. Ruiz-BallesterosBarbara Vizmanos-Lamotte...
    1页
    查看更多>>摘要：Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/ mL; p < 0.04) with higher calcitriol levels (47pg/mL vs. 41.5pg/mL; p = 0.02) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels (r = -0.26; p = 0.001) and urine proteins (mg/dL) (r = -0.39; p<0.01). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count (r = 0.30; p< 0.001) and negatively correlated with the glomerular filtration rate (r = -0.28; p = 0.001). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins (r = 0.38; p< 0.01). The calcidiol deficiency (OR = 2.27; 95% CI= 1.15-4.49; p < 0.01), high calcitriol levels (T3rd, OR = 40.019, 95% CI = 2.23-7.90; p< 0.001), and a high calcitriol/calcidiol ratio score (T3rd, OR = 5.93, 95% CI: 3.08-11.5; p < 0.001) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.
      原文链接:
    • NSTL

    Identifying and Validating an Acidosis-Related Signature Associated with Prognosis and Tumor Immune Infiltration Characteristics in Pancreatic Carcinoma

    Pingfei TangWeiming QuDajun WuShihua Chen...
    1页
    查看更多>>摘要：Background. Acidosis in the tumor microenvironment (TME) is involved in tumor immune dysfunction and tumor progression. We attempted to develop an acidosis-related index (ARI) signature to improve the prognostic prediction of pancreatic carcinoma (PC). Methods. Differential gene expression analyses of two public datasets (GSE152345 and GSE62452) from the Gene Expression Omnibus database were performed to identify the acidosis-related genes. The Cancer Genome Atlas-pancreatic carcinoma (TCGA-PAAD) cohort in the TCGA database was set as the discovery dataset. Univariate Cox regression and the Kaplan-Meier method were applied to screen for prognostic genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish the optimal model. The tumor immune infiltrating pattern was characterized by the single-sample gene set enrichment analysis (ssGSEA) method, and the prediction of immunotherapy responsiveness was conducted using the tumor immune dysfunction and exclusion (TIDE) algorithm. Results. We identified 133 acidosis-related genes, of which 37 were identified as prognostic genes by univariate Cox analysis in combination with the Kaplan-Meier method (p values of both methods < 0.05). An acidosis-related signature involving seven genes (ARNTL2, DKK1, CEP55, CTSV, MYEOV, DSG2, and GBP2) was developed in TCGA-PAAD and further validated in GSE62452. Patients in the acidosis-related high-risk group consistently showed poorer survival outcomes than those in the low-risk group. The 5-year AUCs (areas under the curve) for survival prediction were 0.738 for TCGA-PAAD and 0.889 for GSE62452, suggesting excellent performance. The low-risk group in TCGA-PAAD showed a higher abundance of CD8+ T cells and activated natural killer cells and was predicted to possess an elevated proportion of immunotherapeutic responders compared with the high-risk counterpart. Conclusions. We developed a reliable acidosis-related signature that showed excellent performance in prognostic prediction and correlated with tumor immune infiltration, providing a new direction for prognostic evaluation and immunotherapy management in PC.
      原文链接:
    • NSTL

    Contribution of Gut Microbiota to Immune Tolerance in Infants

    Constanza S. MendezSusan M. BuenoAlexis M. Kalergis
    1页
    查看更多>>摘要：The prevalence of food allergy has increased in recent years, especially among the pediatric population. Differences in the gut microbiota composition between children with FA and healthy children have brought this topic into the spotlight as a possible explanation for the increase in FA. The gut microbiota characteristics are acquired through environmental interactions starting early in life, such as type of delivery during birth and breastfeeding. The microbiota features may be shaped by a plethora of immunomodulatory mechanisms, including a predominant role of Tregs and the transcription factor FOXP3. Additionally, a pivotal role has been given to vitamin A and butyrate, the main anti-inflammatory metabolite. These observations have led to the study and development of therapies oriented to modifying the microbiota and metabolite profiles, such as the use of pre-and probiotics and the determination of their capacity to induce tolerance to allergens that are relevant to FA. To date, evidence supporting these approaches in humans is scarce and inconclusive. Larger cohorts and dose-titration studies are mandatory to evaluate whether the observed changes in gut microbiota composition reflect medical recovery and increased tolerance in pediatric patients with FA. In this article, we discuss the establishment of the microbiota, the immunological mechanisms that regulate the microbiota of children with food allergies, and the evidence in research focused on its regulation as a means to achieve tolerance to food allergens.
      原文链接:
    • NSTL

    Lipopolysaccharide-Induced Transcriptional Changes in LBP-Deficient Rat and Its Possible Implications for Liver Dysregulation during Sepsis

    Zhixiang HeZichen SongLeilei MengWenhui Cheng...
    1页
    查看更多>>摘要：Sepsis is an organ dysfunction caused by the dysregulated inflammatory response to infection. Lipopolysaccharide-binding protein (LBP) binds to lipopolysaccharide (LPS) and modulates the inflammatory response. A rare systematic study has been reported to detect the effect of LBP gene during LPS-induced sepsis. Herein, we explored the RNA sequencing technology to profile the transcriptomic changes in liver tissue between LBP-deficient rats and WT rats at multiple time points after LPS administration. We proceeded RNA sequencing of liver tissue to search differentially expressed genes (DEGs) and enriched biological processes and pathways between WT and LBP-deficient groups at 0h, 6h, and 24h. In total, 168, 284, and 307 DEGs were identified at 0h, 6h, and 24h, respectively, including Lrp5, Cyp7a1, Nfkbiz, Sigmar1, Fabp7, and Hao1, which are related to the inflammatory or lipid-related process. Functional enrichment analysis revealed that inflammatory response to LPS mediated by Ifng, Cxcl10, Serpine1, and Lbp was enhanced at 6h, while lipid-related metabolism associated with C5, Cyp4a1, and Eci1 was enriched at 24 h after LPS administration in the WT samples. The inflammatory process was not found when the LBP gene was knocked out; lipid-related metabolic process and peroxisome proliferator-activated receptor (PPAR) signaling pathway mediated by Dhrs7b and Tysnd1 were significantly activated in LBP-deficient samples. Our study suggested that the invading LPS may interplay with LBP to activate the nuclear factor kappa B (NF-κB) signaling pathway and trigger uncontrolled inflammatory response. However, when inhibiting the activity of NF-κB, lipid-related metabolism would make bacteria removal via the effect on the PPAR signaling pathway in the absence of LBP gene. We also compared the serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels using the biochemistry analyzer and analyzed the expression of high mobility group box 1 (HMGB1) and cleaved-caspase 3 with immunohistochemistry, which further validated our conclusion.
      原文链接:
    • NSTL

    Knockdown of lncRNA CCAT1 Inhibits the Progression of Colorectal Cancer via hsa-miR-4679 Mediating the Downregulation of GNG10

    Ning WangJun LiJu HeYong-Guang Jing...
    1页
    查看更多>>摘要：Great concerns have raised crucial roles of long noncoding RNAs (lncRNAs) on colorectal cancer progression due to the increasing number of studies in cancer development. Previous studies reveal that lncRNA CCAT1 plays an important role in the progression of a variety of cancers. However, the role of lncRNA CCAT1 in colorectal cancer is still unclear. In this study, we found that in both colorectal tissues and cell lines the level of lncRNA CCAT1 was increased. Downregulation of lncRNA CCAT1 inhibited the proliferation, migration, and invasion of colorectal cell lines and promoted apoptosis. We then found that hsa-miR-4679 could bind to lncRNA CCAT1 directly, and with further functional analyses, we confirmed that lncRNA CCAT1 sponged hsa-miR-4679 to promote the progression of colorectal cancer. Next, we found that hsa-miR-4679 was directly bound to 3 UTR of GNG10 (guanine nucleotide-binding protein, gamma 10). GNG10 overexpression promoted the progression of colorectal cancer, and this phenotype could be reversed by miR-4679 mimics. At last, we knocked down CCAT1 in vivo and found that sh-CCAT1 reduced the tumor size and the number of proliferating cells. In summary, our findings revealed that lncRNA CCAT1 facilitated colorectal cancer progression via the hsa-miR-4679/GNG10 axis and provided new potential therapeutic targets for colorectal cancer.
      原文链接:
    • NSTL

    HOXA-AS3 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells via the miR-455-5p/PD-L1 Axis

    Cheng ZengShaojun YeYu ChenQu Zhang...
    1页
    查看更多>>摘要：Hepatocellular carcinoma (HCC) is the most prevalent type of hepatic carcinoma. Long noncoding RNAs (lncRNAs) are considered crucial regulators of gene expression; however, their functions in HCC are not well understood. Thus, the present study is aimed at elucidating the functions of the lncRNA HOXA-AS3 in HCC. The functions of the HOXA-AS3/miR-455-5p/ programmed death-ligand 1 (PD-L1) axis were investigated in vitro via qRT-PCR and dual-luciferase reporter assays. The effect of HOXA-AS3 expression on tumor growth and metastasis was assessed using a mouse xenograft model. High HOXA-AS3 expression was observed in the HCC cell lines. Furthermore, overexpression of HOXA-AS3 in HCC cells enhanced proliferation, migration, and invasion, regulated the cell cycle, and retarded apoptosis. We also identified an miR-455-5p binding site in HOXA-AS3. By sponging miR-455-5p, HOXA-AS3 increased the expression of PD-L1. Additionally, both the inhibition of PD-L1 and overexpression of miR-455-5p reversed the effects on cell proliferation and invasion triggered by the overexpression of HOXA-AS3. In conclusion, HOXA-AS3 modulated the functions of HCC cells through the miR-455-5p/PD-L1 axis. Therefore, HOXA-AS3 may be a novel therapeutic target for HCC.
      原文链接:
    • NSTL

    New Insights into Immune-Based Diagnosis, Therapy and Prophylaxis for Infectious Diseases 2020

    Giuseppe A. SauttoRoberta A. DiottiKristen M. Kahle
    1页
    查看更多>>摘要：Immune-based diagnostic, therapeutic, and prophylactic tools have played a central role in medicine since the discovery of antibodies at the end of the 19th century. Since then, more and more sophisticated antibody-based approaches have been developed allowing to easily diagnose different types of disorders spanning from infectious diseases to premalignant, malignant, and autoimmune diseases. As an example, the enzyme-linked immunosorbent assay (ELISA) represents one of the simplest but still most powerful methods for the diagnosis of different types of diseases, and thanks to its versatility, multiple formats have been developed such as the competitive ELISA, the sandwich ELISA, and the indirect ELISA. Additionally, besides assessing the binding to an antigen, antibody-based method approaches can also have a prognostic value since they can assess the presence, for example, of neutralizing antibodies eliciting a protective effect. In this regard, the hemagglutination inhibition assay (HAI) represents the gold standard method to evaluate the efficacy of not only current standard of care but also underdevelopment next-generation influenza vaccines in eliciting a neutralizing and protective immune response. As for ELISA, the HAI has also been developed in different formats in order to dissect the antibody response, for example, following influenza infection or vaccination. In this context, our group recently described a competitive HAI-based assay using a combination of influenza virus and recombinant influenza hemagglutinin (HA) proteins to dissect the HAI functional activity of HA-specific antibody populations in a single assay format [1].
      原文链接:
    • NSTL