Inflammation plays a critical role in the development of severe neonatal morbidities. Myeloid-derived suppressor cells (MDSCs) were recently implicated in the regulation of immune responses in newborns. Here, we report that the presence of MDSCs and their functional activity in infants are closely associated with the maturity of newborns and the presence of lactoferrin (LF) in serum. Low amounts of MDSCs at birth predicted the development of severe pathology in preterm infants — necrotizing enterocolitis (NEC). In vitro treatment of newborn neutrophils and monocytes with LF converted these cells to MDSCs via the LRP2 receptor and activation of the NF-κB transcription factor. Decrease in the expression of LRP2 was responsible for the loss of sensitivity of adult myeloid cells to LF. LF-induced MDSCs (LF-MDSCs) were effective in the treatment of newborn mice with NEC, acting by blocking inflammation, resulting in increased survival. LF-MDSCs were more effective than treatment with LF protein alone. In addition to affecting NEC, LF-MDSCs demonstrated potent ability to control ovalbumin-induced (OVA-induced) lung inflammation, dextran sulfate sodium–induced (DSS-induced) colitis, and concanavalin A–induced (ConA-induced) hepatitis. These results suggest that cell therapy with LF-MDSCs may provide potent therapeutic benefits in infants with various pathological conditions associated with dysregulated inflammation.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease. The dysregulated immune system plays an important role in the pathogenesis of AS. Myeloid-derived suppressor cells (MDSCs) play a key immunoregulatory role in autoimmune arthritis. The aim of this study was to clarify the underlying immunoregulatory mechanism of MDSCs in patients with AS. Flow cytometry was used to analyze the phenotype of MDSCs among peripheral blood mononuclear cells (PBMCs) from 46 patients with AS and 46 healthy control subjects. The correlation between MDSC frequency and the disease index of patients with AS was evaluated. A T cell proliferation experiment was used to evaluate the immunosuppressive function of MDSCs. Polymorphonuclear (PMN) and monocytic (M)-MDSCs were significantly elevated in the PBMCs of patients with AS, when compared with levels in healthy controls. Additionally, M-MDSC levels correlated positively with the clinical index of AS, including the Bath ankylosing spondylitis disease activity index (BASDAI) score, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. M-MDSCs derived from patients with AS suppressed T cell responses, and this effect was dependent on the induction of arginase-I. Furthermore, AS-derived M-MDSCs showed high levels of phosphorylated STAT3. Stattic, a STAT3-specific inhibitor, and STAT3-targeted siRNA abrogated the immunosuppressive function of M-MDSCs. Inhibition of STAT3 signaling also resulted in decreased arginase-I activity. STAT3/arginase-I signaling plays an important role in both the expansion and activation of M-MDSCs in patients with AS. This information may be beneficial in developing novel therapeutic strategies for preventing AS.

Prognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein–protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation. Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.

Background: Sphingosine-1-phosphate receptor (S1PR1) is involved in vascular development, a key process in tumorigenesis. This study aimed to evaluate its roles in tumor development and prognosis. Methods: S1PR1 expression levels were analyzed using TIMER and Oncomine database, and the prognostic significance of S1PR1 was assessed using PrognoScan and Kaplan-Meier plotter databases. The relationship between S1PR1 and tumor-infiltrated immune cells was analyzed using TIMER. Results: S1PR1 expression was remarkably lower in breast and lung cancer tissues than in the corresponding normal tissues. Lower expression was related to poor overall survival and disease-free survival in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). A functional network analysis confirmed the function of S1PR1 in regulating vasculogenesis. In addition, S1PR1 levels were significantly negative with regard to the tumor purity of BRCA (r = − 0.508, P = 1.76e-66), LUAD (r = − 0.353, P = 6.05e-16), and LUSC (r = − 0.402, P = − 5.20e-20). Furthermore, S1PR1 levels were significantly positive with regard to infiltrating CD8⁺ (r = 0.38, P = 5.91e-35) and CD4⁺ T cells (r = 0.335, P = 1.03e-26), macrophages (r = 0.219, P = 3.67e-12), neutrophils (r = 0.168, P = 2.03e-7), and dendritic cells (DCs) (r = 0.208, P = 9.14e-11) in BRCA; S1PR1 levels were significantly positive with regard to CD8⁺ T cells (r = 0.308, P = 3.61e-12), macrophages (r = 0.376, P = 1.01e-17), neutrophils (r = 0.246, P = 4.15e-8), and DCs (r = 0.207, P = 4.16e-6) in LUAD; and positive with regard to B cells (r = 0.356, P = 1.57e-15), CD8⁺ (r = 0.459, P = 3.83e-26) and CD4⁺ T cells (r = 0.338, P = 3.98e-14), macrophages (r = 0.566, P = 2.61e-45), neutrophils (r = 0.453, P = 1.79e-25), and DCs (r = 0.56, P = 2.12e-40) in LUSC. Conclusions: S1PR1 levels are positively correlated with multiple immune markers in breast and lung cancer. These observed correlations between S1PR1 and the prognosis and immune cell infiltration provide a foundation for further research on its immunomodulatory role in cancer.

Objective: Patients with necrotizing enterocolitis display severe gastrointestinal complications of prematurity, but the mechanism driving this clinical profile remains unknown. We used mass cytometry time-of-flight to characterize and compare immune cell populations in the blood and intestine tissue from patients with and without (controls) necrotizing enterocolitis at single-cell resolution.Methods: We completed a deep mapping of the immune system of the peripheral blood mononuclear cells and intestinal mucosa tissue using mass cytometry to evaluate immune cell types, which revealed global immune dysregulation characteristics underlying necrotizing enterocolitis.Results: Compared with controls, natural killer cells display signs of heightened activation and increased cytotoxic potential in the peripheral blood and mucosa of patients with necrotizing enterocolitis. Furthermore, CD4⁺ T effector memory cells, non-classical monocytes, active dendritic cells, and neutrophils were specifically enriched in the mucosa, suggesting trafficking from the periphery to areas of inflammation. Moreover, we mapped the systemic and local distinct immune signatures suggesting patterns of cell localization in necrotizing enterocolitis.Conclusion: We used mass cytometry time-of-flight technology to identify immune cell populations specific to the peripheral blood and intestinal mucosa tissue from patients with necrotizing enterocolitis and controls. This information might be used to develop precise diagnosis and therapies that target specific cell populations in patients with necrotizing enterocolitis.