Gutierrezkrogsgaard2976

Tumor cells influencing the microenvironment are essential for restrained immunity in head and neck squamous cell carcinoma (HNSCC). There has been considerable progress in the research on monoclonal antibodies for antigen-specific immunotherapy that overcome immunosuppressive checkpoint receptor/ligand signaling in patients with HNSCC. However, alteration of immunogenicity and formation of neoantigens that lead to dysregulation and immunosuppression in the HNSCC microenvironment is not well-defined. The aim of this study was to quantify the Immune, Stromal, and ESTIMATE scores based on the gene matrix of patients with HNSCC reported in The Cancer Genome Atlas (TCGA). We examined the association of the Immune, Stromal, and ESTIMATE scores with the pathologic characteristics of patients with HNSCC, using weighted gene co-expression network (WGCNA) and protein-protein interaction (PPI) analyses, and selected 17 hub gene signatures from the key gene module that was mostly correlated to immunocyte infiltration. Gene functional enrichment showed that this key gene module was closely related to the regulation of immune cell activation and its relevant pathways. In the prognostic analysis, high expression of CD3E, SASH3, CD2, SIRPG, UBASH3A, IKZF1, SPN, IL10RA, SLA, and CD3G was significantly associated with a good prognosis. Consequently, these prognosis-related genes were validated via analysis of mRNA expression in tumor-infiltrating lymphocytes (TILs) and matched peripheral blood lymphocytes (PBLs) in ten patients with HNSCC, and the expression of these genes was significantly higher in TILs compared to that in PBLs. These findings provide a novel understanding of the tumor immune targets for improved therapeutic regimes in patients with HNSCC.

Treatment options for recurrent glioblastoma (rGBM) remain scarce, which may be due to the limited understanding of its molecular characteristics.

Based on gene expression profiling, the infiltration scores of 26 immune cell types were calculated using gene set variation analysis. The differences between rGBM and other cancer subtypes were estimated to characterize the specific immune characteristics of rGBM, and the prognostic value of immune cells in rGBM was estimated using univariate and multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were performed to identify whether CD8 T-cell infiltration could be useful in selecting treatment options for rGBM patients.

We found that rGBM patients were associated with enrichment of activated CD8 T cells, and high CD8 T-cell infiltration was associated with superior overall survival. EGFR signaling pathway Patients exhibiting high CD8 T-cell infiltration who received treatment with bevacizumab and lomustine combination therapy experienced a significant benefit in overall survival and progression-free survival, whereas patients with low CD8 T-cell infiltration did not experience such a benefit. CD8 T cells remained an independent prognostic factor in multivariate analyses (cohort 1 hazard ratio [HR]=0.546, 95% confidence interval [CI] 0.316-0.945, P=0.031; cohort 3 HR=0.615, 95% CI 0.387-0.978, P=0.040) after adjusting for clinicopathological and molecular factors.

Activated CD8 T-cells is a promising biomarker for predicting overall survival in rGBM patients and could be used for assisting treatment selection.

Activated CD8 T-cells is a promising biomarker for predicting overall survival in rGBM patients and could be used for assisting treatment selection.

Behcet's disease (BD) is an autoimmune disorder with the serious possibility of blindness, calling for further research on its pathogenesis. Our aim was to study the metabolite composition of sweat in BD and to identify possible biomarkers.

Metabolomics analysis was performed on sweat samples from 20 BD patients and 18 normal controls by liquid chromatography tandem mass spectrometry.

A significantly different metabolic profile of sweat was observed when BD patients were compared with healthy controls. The result of the orthogonal partial least squared-discrimination analysis (OPLS-DA) showed that these two comparison groups could be separated with a relatively satisfactory fitting degree (R2Y=0.995 and Q2=0.817 in positive ion mode; R2Y=0.991 and Q2=0.721 in negative ion mode). Based on OPLS-DA, a panel of metabolites was selected as candidate biomarkers, including l-citrulline, l-pyroglutamic acid, urocanic acid, 2-oxoadipic acid, cholesterol 3-sulfate, and pentadecanoic acid.

This is the first report on the metabolite profile of sweat in BD. Our results demonstrated a significantly different metabolite composition of sweat in BD compared to that of healthy controls.

This is the first report on the metabolite profile of sweat in BD. Our results demonstrated a significantly different metabolite composition of sweat in BD compared to that of healthy controls.Specialized metabolites are essential components in plant defence systems, serving as signalling molecules and chemical weapons against pathogens. The manipulation of plant defence metabolome or metabolites can thus be an important virulence strategy for pathogens. Because of their central role, metabolites can give valuable insights into plant-pathogen interactions. Here, we have conducted nontargeted metabolite profiling with UPLC-ESI-qTOF-MS to investigate the metabolic changes that have taken place in the crown tissue of Fragaria vesca L. (woodland strawberry) and Fragaria × ananassa (Weston) Duchesne ex Rozier (garden strawberry) during 48 h after Phytophthora cactorum challenge. Two P. cactorum isolates were compared Pc407 is highly virulent to F. × ananassa and causes crown rot, whereas Pc440 is mildly virulent. In total, 45 metabolites differentially accumulated between the treatment groups were tentatively identified. Triterpenoids and various lipid compounds were highly represented. The levels of several triterpenoids increased upon inoculation, some of them showing distinct accumulation patterns in different interactions. Triterpenoids could either inhibit or stimulate P. cactorum growth and, therefore, triterpenoid profiles might have significant impact on disease progression. Of the lipid compounds, lysophospholipids, linoleic acid and linolenic acid were highly accumulated in the most compatible Pc407 - F. × ananassa interaction. As lysophospholipids promote cell death and have been linked to susceptibility, these compounds might be involved in the pathogenesis of crown rot disease. This metabolite analysis revealed potential factors contributing to the outcome of P. cactorum - strawberry interactions. The information is highly valuable, as it can help to find new breeding strategies and new solutions to control P. cactorum in strawberry.