Themis: advancing precision oncology through comprehensive molecular subtyping and optimization.

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces 'Themis' (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies.

Prmt5 deficiency inhibits CD4+ T-cell Klf2/S1pr1 expression and ameliorates EAE disease.

Background: Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated.

Methods: EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35-55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5, Prmt5cko) and Prmt5 (WT) mice.

Prmt5 deficient mouse B cells display RNA processing complexity and slower colorectal tumor progression.

Protein arginine methyltransferase 5 (Prmt5) is essential for normal B-cell development; however, the roles of Prmt5 in tumor-infiltrating B cells in tumor therapy have not been well elucidated. Here, we revealed that CD19-cre-Prmt5 (Prmt5cko) mice showed smaller tumor weights and volumes in the colorectal cancer mouse model; B cells expressed higher levels of Ccl22 and Il12a, which attracted T cells to the tumor site. Furthermore, we used direct RNA sequencing to comprehensively profile RNA processes in Prmt5 deletion B cells to explore underline mechanisms.

Urinary exosomal long non-coding RNAs as noninvasive biomarkers for diagnosis of bladder cancer by RNA sequencing.

Introduction: Cystoscopy is the standard methodology for diagnosis of bladder cancer (BC), but it is invasive and relatively expensive. Previous studies have found that urinary exosomal long non-coding RNAs (lncRNAs) may act as potential noninvasive biomarkers for diagnosis. Here we identified urinary exosomal lncRNAs that are differentially expressed between BC and controls, and established a panel for diagnosis of BC.

PD-L1CD8 T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance.

Immunotherapy targeting checkpoint blockade to rescue T cells from exhaustion has become an essential therapeutic strategy in treating cancers. Till now, little is known about the PD-L1 graphic pattern and characteristics in CD8 T cells. We combined cytometry by time-of-flight (CyTOF) and imaging mass cytometry (IMC) approaches to analyze CD8 T cells from primary lung cancers and discovered that PD-L1CD8 T cells were enriched in tumor lesions, spatially localized with PD-1CD8 T cells.

PRMT5 Inhibition Promotes PD-L1 Expression and Immuno-Resistance in Lung Cancer.

Protein arginine transferase 5 (PRMT5) has been implicated as an important modulator of tumorigenesis as it promotes tumor cell proliferation, invasion, and metastasis. Studies have largely focused on PRMT5 regulating intrinsic changes in tumors; however, the effects of PRMT5 on the tumor microenvironment and particularly immune cells are largely unknown. Here we found that targeting PRMT5 by genetic or pharmacological inhibition reduced lung tumor progression in immunocompromised mice; however, the effects were weakened in immunocompetent mice.

PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1CD8 Terminal Effector T Cells and Promotes Cancer Development.

Protein arginine methyltransferase 5 (PRMT5) participates in the symmetric dimethylation of arginine residues of proteins and contributes to a wide range of biological processes. However, how PRMT5 affects the transcriptional and epigenetic programs involved in the establishment and maintenance of T cell subset differentiation and roles in antitumor immunity is still incompletely understood. In this study, using single-cell RNA and chromatin immunoprecipitation sequencing, we found that mouse T cell-specific deletion of PRMT5 had greater effects on CD8 than CD4 T cell development, enforcing CD8 T cell differentiation into Klrg1 terminal effector cells.

Decreased expression of ATF3, orchestrated by β-catenin/TCF3, miR-17-5p and HOXA11-AS, promoted gastric cancer progression via increased β-catenin and CEMIP.

ATF3 has been reported to be dysregulated in various cancers and involved in various steps of tumorigenesis. However, the mechanisms underlying the abnormal expression of ATF3 and its biological function in gastric cancer (GC) have not been well investigated. Here, we report ATF3 as one of the key regulators of GC development and progression.

PRMT5 disruption drives antitumor immunity in cervical cancer by reprogramming T cell-mediated response and regulating PD-L1 expression.

: Protein arginine methyltransferase 5 (PRMT5) is an oncogene that promotes tumor cell proliferation, invasion and metastasis. However, the underlying mechanisms by which PRMT5 contributes to the progression of cervical cancer and especially the tumor microenvironment remain poorly understood. : PRMT5 expression level was analyzed by Q-PCR, western blot, immunohistochemistry, and TCGA database.

Interleukin 32 Promotes Foxp3 Treg Cell Development and CD8 T Cell Function in Human Esophageal Squamous Cell Carcinoma Microenvironment.

Proinflammatory cytokine interleukin 32 (IL-32) is involved in infectious diseases and cancer, but what subtypes of immune cells express IL-32 and its roles in tumor microenvironment (TME) have not been well discussed. In this study, we applied bioinformatics to analyze single-cell RNA sequencing data about tumor-infiltrating immune cells from esophageal squamous cell carcinoma (ESCC) TME and analyzed IL-32 expression in different immune cell types. We found CD4 regulatory T cells (Treg cells) express the highest level of IL-32, while proliferating T and natural killer cells expressed relatively lower levels.

Mechanisms for propofol in inhibiting the proliferation and invasion of glioma U87 cells and its effect on miR-134 expression.

Objectives: To investigate the effects of propofol on the proliferation and invasion of glioma U87 cells and to explore the possible anti-tumor mechanisms.

Methods: The glioma U87 cells was divided into a blank group, a positive control group, and the propofol groups (1.00, 2.

Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME.

Gastric cancer-secreted exosomal X26nt increases angiogenesis and vascular permeability by targeting VE-cadherin.

Angiogenesis is closely associated with tumorigenesis, invasion, and metastasis by providing oxygen and nutrients. Recently, increasing evidence indicates that cancer-derived exosomes which contain proteins, coding, and noncoding RNAs (ncRNAs) were shown to have proangiogenic function in cancer. A 26-nt-long ncRNA (X26nt) is generated in the process of inositol-requiring enzyme 1 alpha (IRE1α)-induced unspliced XBP1 splicing.

BACH2 regulates the function of human CD4 CD45RA Foxp3 ° cytokine-secreting T cells and promotes B-cell response in systemic lupus erythematosus.

Although CD4 CD45RA Foxp3 ° cytokine-secreting T cells (Fr.III cells) have been reported to be increased in systemic lupus erythematosus (SLE), their function and effects on response of B cells are still unclear. Here, we dissect how BACH2 regulates Fr.

Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies.

Background: Serum/plasma YKL-40 can be a useful index that is associated with tumor development. However, the prognostic value of serum/plasma YKL-40 in patients with solid tumors is still unclear. We aimed to utilize the existing literature to investigate the prognostic value of serum/plasma YKL-40 in solid tumors.

DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation.

Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion.

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population.

Background: ICG-001, a small molecule, binds CREB-binding protein (CBP) to disrupt its interaction with β-catenin and inhibits CBP function as a co-activator of Wnt/β-catenin-mediated transcription. Given its ability to inhibit Wnt/β-catenin signaling pathway, ICG-001 has been used in some tumor types to exert its anticarcinogenic effect. Here, we examined ICG-001 and its potential role as a therapeutic in gastric cancer (GC).

miR-155 Regulates IL-10-Producing CD24CD27 B Cells and Impairs Their Function in Patients with Crohn's Disease.

Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in preventing and curing autoimmune diseases in experimental mouse models. However, the precise cellular and molecular mechanisms of action of B10 cells in humans, especially in patients with Crohn's disease (CD), remain to be determined. miR-155 regulates many physiological and pathological conditions, including inflammation such as that in CD.

Protein Arginine Methyltransferase 5 Inhibition Upregulates Foxp3 Regulatory T Cells Frequency and Function during the Ulcerative Colitis.

Ulcerative colitis (UC) pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3 regulatory T cells (Tregs) plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs) regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms.

Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3.

IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin-12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer.

Modulation of STAT3 and STAT5 activity rectifies the imbalance of Th17 and Treg cells in patients with acute coronary syndrome.

The signal transducer and activator of transcription (STAT) activity plays an important role in the differentiation and imbalance of Th17 and Treg cells in acute coronary syndrome (ACS) patients. We determined that the basal STAT3 phosphorylation level was significantly increased and exhibited a positive relationship with Th17 cells but was negatively correlated with Treg cells in ACS patients. Opposite effects were observed for STAT5 activity.

TNFα promotes Th17 cell differentiation through IL-6 and IL-1β produced by monocytes in rheumatoid arthritis.

TNFα plays an important role in autoimmune pathogenesis and is the main therapeutic target of rheumatoid arthritis. However, its underlying mechanism is not completely understood. In this study, we described that Th17 cells were accumulated in synovial fluid, which was attributable to TNFα aberrantly produced in rheumatoid synovium.

Imbalanced frequencies of Th17 and Treg cells in acute coronary syndromes are mediated by IL-6-STAT3 signaling.

Aims: Extensive evidence suggests inflammatory components participate in the pathogenic processes of acute coronary syndromes (ACS). In this study, we aimed to elucidate the role and mechanism underlying the imbalance of Th17 and Treg cell peripheral populations in the pathogenesis of ACS.

Methods And Results: Using a flow cytometric analysis, we observed a significantly increased frequency of Th17 cells and a concurrently decreased CD4(+)CD25(+)Foxp3(+) Treg cells in patients with ACS.

Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis.

Regulatory T (Treg) cells suppress autoimmune disease, and impaired Treg cell function is associated with rheumatoid arthritis. Here we demonstrate that forkhead box P3 (FOXP3) transcriptional activity and, consequently, Treg cell suppressive function are regulated by phosphorylation at Ser418 in the C-terminal DNA-binding domain. In rheumatoid arthritis-derived Treg cells, the Ser418 site was specifically dephosphorylated by protein phosphatase 1 (PP1), whose expression and enzymatic activity were induced in the inflamed synovium by tumor necrosis factor α (TNF-α), leading to impaired Treg cell function.