Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated cancer patients who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DCs). VitE entered DCs via SCARB1 receptor and restored tumor-associated DCs' functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically, or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and DC-derived extracellular vesicles (DC-EVs) triggering systemic antigen-specific T cell antitumor immunity. Combining VitE with DC-recruiting cancer vaccines, or immunogenic chemotherapies, greatly boosted ICT efficacy in animals. Therefore, combining VitE supplement, or SHP1-inhibited DCs/DC-EVs, with DCs-enrichment therapies could substantially augment T cell antitumor immunity and enhance the efficacies of cancer immunotherapies.
Background. Micronutrient powder is a potential strategy to improve iron status and reduce anemia in refugee populations.Objective. Results. At the baseline, midline, and endline visits, respectively, the mean (± SE) hemoglobin concentration in women was 121.4 ± 0.8, 120.8 ± 0.9, and 120.6 ± 1.0 g/L (p = .42); the prevalence of anemia (hemoglobin < 120 g/L) was 42. 6%, 41.3%, and 41.7% (p = .92); and the mean soluble transferrin receptor concentration was 24.1 ± 0.5, 20.7 ± 0.7, and 20.8 ± 0.7 nmol/L (p = .0006). In children, the mean hemoglobin concentration was 105.7 ± 0.6, 109.0 ± 1.5, and 105.5 ± 0.3 g/L (p = .95), respectively; the prevalence of anemia (hemoglobin < 110 g/L) was 55. 5%, 52.3%, and 59.8% (p = .26); and the mean soluble transferrin receptor concentration was 36.1 ± 0.7, 29.5 ± 1.9, and 28.4 ± 3.2 nmol/L (p = .02), in models that were adjusted for age using least squares means regression.Conclusions. In children and in women of childbearing age, the availability of micronutrient powder was associated with a small improvement in iron status but no significant change in hemoglobin in this refugee camp setting.
The IC53 gene was reported to be upregulated in the colon adenocarcinoma cell line SW480. Here, we show that the expression level of IC53 is positively correlated with the grade and depth of invasion in adenocarcinoma of the colon. Injection of IC53 stably transfected HCT-116 cells into athymic nude mice promoted tumor growth. Furthermore, overexpression of IC53 increased cell invasive growth, which could be dramatically prevented by knocking down IC53 with siRNA. The effects of IC53 on cellinvasive growth were mediated by upregulation of integrins, activation of phosphatidylinositol 3-kinase and phosphorylation of Akt. A single-nucleotide polymorphism rs2737 in the IC53 gene created a potential microRNA379 target site, and microRNA379 expression inhibited IC53 translation. Among 222 patients with colorectal cancer, the C/C rs2737 genotype was associated with late onset of colorectal cancer (median age 63.0 versus 55.3 years, P = 0.003). The frequency of the C/C rs2737 genotype was much lower in patients who developed colorectal cancer below the age of 45 years than in individuals over age 45 years (10.8% versus 26.6%, P = 0.039). These data indicated that IC53 is a positive mediator for colon cancer progression, and IC53-rs2737 may serve as protection from the onset of colorectal cancer.
Backgroud:Suppressors of cytokine signaling (SOCS) family play important roles in the development of cancers by inhibiting the transmission of the Janus kinases–signal transducers and activators of transcription (JAK-STAT) signaling pathway. However, the expression patterns and prognostic value of SOCS family genes in non-small cell lung cancer (NSCLC) remains unclear. Methods: The SOCS family genes expression profiles were explored using ONCOMINE and GEPIA online tools. The mutation and copy number alterations of SOCS family genes in NSCLC were assessed by cBioportal for Cancer Genomics. The methylation status of SOCS family members were analyzed through MEXPRESS and UCSC Xena website. The prognostic values of SOCS family genes in NSCLC were explored through Kaplan-Meier Plotter database. Results: The expression levels of SOCS2, SOCS3, and cytokine-inducible SH2-containing protein (CIS/CISH) were significantly reduced in NSCLC tissues compared to normal lung tissues. The aberrant DNA methylation of SOCS family genes were frequent in NSCLC. CISH methylation was negatively correlated with gene expression in NSCLC. The Kaplan-Meier Plotter analysis demonstrated high expression of SOCS1 may be a predictor of poor prognosis in lung adenocarcinoma(LUAD) but served as a favorable prognostic marker of lung squamous cell carcinoma. The high expression levels of SOCS2 and SOCS4-7 were significantly correlated with better overall survival (OS) in LUAD but not in lung squamous carcinoma (LUSC) patients. Conclusions:Our findings indicated that the aberrant gene expression and DNA methylation of SOCS family members are common in NSCLC and contribute to tumorigenesis. SOCS family genes may serve as therapeutic targets and prognostic biomarkers for NSCLC patients
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