IFN-α/ß/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype.

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/ß/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/ß/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/ß/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/ß/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.

Targeting the Notch signaling pathway and the Notch ligand, DLL3, in small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive and poorly differentiated cancer with high-grade neuroendocrine (NE) features, accounting for approximately 15 % of all lung cancers. For decades, chemotherapy and radiotherapy have predominated the treatment strategy for SCLC, but relapses ensue quickly and result in poor survival of patients. Immunotherapy has brought novel insights, yet the efficacy is still restricted to a limited population with SCLC. Notch signaling is identified to play a key role in the initiation and development of SCLC, and the Notch ligand, Delta-like ligand 3 (DLL3) is found broadly and specifically expressed in SCLC cells. Thus, Notch signaling is under active exploration as a potential therapeutic target in SCLC. Herein, we summarized and updated the functional relevance of Notch signaling in SCLC, discussed Notch signaling-targeted therapy for SCLC and the correspondent preclinical and clinical trials, and investigated the promising synergy effects of Notch signaling targeted therapy and immune checkpoint inhibitors (ICIs) treatment.

Effect of acute exposure to hypobaric hypoxia on learning and memory in adult Sprague-Dawley rats.

The present study aimed to observe the effects of acute exposure to hypobaric hypoxia on learning and memory in adult Sprague-Dawley (SD) rats as well as the changes in N-methyl-D-aspartate receptor (NMDAR) subunits. Learning and memory abilities were evaluated with Morris water maze following simulated hypoxia at 5000 m or 7000 m for 2, 4 or 6 days. The number of red blood cells, the level of hemoglobin, oxidative stress markers, the extent of neuronal damage in the hippocampal CA1, and the expression of NMDAR subunits were all measured. In place navigation test, the escape latency significantly increased only in the 5000 M 6Day (P < 0.05) group than the latency in the plain group on the fourth day. In the spatial probe test, the times of platform passing showed no significant difference between the hypoxia and plain groups. Polycythemia, an increased ratio of superoxide dismutase/malondialdehyde and degeneration of neurons appeared in an elevation-dependent and duration-dependent manner in those hypoxia groups. Furthermore, the protein expression of NR1 increased and the protein expression levels of NR2A, NR2B, and NR3A were all decreased in the 5000M 6Day and 7000M 6Day groups. In summary, the feeble effect of acute exposure to simulated hypobaric hypoxia on learning and memory in adult SD rats may be attributed to increased antioxidative capacities and decreased expression of NR3A. And moreover, differences in the expressions of NMDAR subunits were closely related to the altitude and duration.

[Association of tumor necrosis factor-alpha gene polymorphisms with Henoch-Schonlein purpura nephritis in children].

OBJECTIVE: To study the relationship of tumor necrosis factor-alpha (TNF-α)-308G/A gene polymorphisms with Henoch-Schonlein purpura nephritis (HSPN) in children. METHODS: Using the direct DNA sequencing method, polymorphisms in the TNF-α promoter region (-308) were genotyped in 110 Han children with Henoch-Schonlein purpura (HSP group), including 52 children with nephritis and 58 children without nephritis. Plasma TNF-α levels were measured using ELISA. Ninety ethnically matched healthy children were used as the control group. RESULTS: There were no significant differences in the polymorphisms of TNF-α (-308G/A) between the HSP and control groups (P>0.05). The GA genotype (29% vs 10%) and A allele frequency (18% vs 7%) in HSP children with nephritis (HSPN) were more common than in those without nephritis (P<0.05). Plasma TNF-α levels in HSPN children with GA+AA genotype (7.1±2.3 pg/mL) were significantly higher than those with GG genotype (5.7±1.5 pg/mL) (P<0.05). CONCLUSIONS: TNF-α-308GA genotype and A allele may contribute to the increased risk for the development of nephritis in children with HSP.