Polyunsaturated fatty acids promote M2-like TAM deposition via dampening RhoA-YAP1 signaling in the ovarian cancer microenvironment.

Background: Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive.

HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage.

Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection.

Identifying the Spatial Architecture That Restricts the Proximity of CD8 T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma.

The anti-tumor function of CD8 T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8 T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8 T cells in human pancreatic ductal adenocarcinoma (PDAC).

Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-α in rheumatoid arthritis.

Objectives: B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases.

SUMOylation of the ubiquitin ligase component KEAP1 at K39 upregulates NRF2 and its target function in lung cancer cell proliferation.

Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is important for the expression of genes associated with oxidative stress. The levels of NRF2 are controlled by Kelch-like ECH-associated protein 1 (KEAP1)-dependent degradation. Although oxidative stress is known to suppress KEAP1 activity to stabilize the levels of NRF2, the mechanism for this control is unclear.

Identification of calcium and integrin-binding protein 1 as a reprogrammed glucose metabolism mediator to restrict immune cell infiltration in the stromal compartment of pancreatic ductal adenocarcinoma.

An increasing body of evidence has suggested that reprogrammed metabolism plays a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC) by affecting the tumor and stromal cellular components in the tumor microenvironment (TME). By analyzing the KRAS pathway and metabolic pathways, we found that calcium and integrin-binding protein 1 (CIB1) corresponded with upregulation of glucose metabolism pathways and was associated with poor prognosis in patients with PDAC from The Cancer Genome Atlas (TCGA). Elevated CIB1 expression combined with upregulated glycolysis, oxidative phosphorylation (Oxphos), hypoxia pathway activation, and cell cycle promoted PDAC tumor growth and increased tumor cellular com-ponents.

PD-1CD8 T Cells Proximal to PD-L1CD68 Macrophages Are Associated with Poor Prognosis in Pancreatic Ductal Adenocarcinoma Patients.

Immune complexity status in the TME has been linked to clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. TME assessments with current cell marker and cell density-based analyses do not identify the original phenotypes of single cells with multilineage selectivity, the functional status of the cells, or cellular spatial information in the tissues. Here, we describe a method that circumvents these problems.

Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis.

Background: Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood.

Methods: PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication.

Survival prediction of stomach cancer using expression data and deep learning models with histopathological images.

Accurately predicting patient survival is essential for cancer treatment decision. However, the prognostic prediction model based on histopathological images of stomach cancer patients is still yet to be developed. We propose a deep learning-based model (MultiDeepCox-SC) that predicts overall survival in patients with stomach cancer by integrating histopathological images, clinical data, and gene expression data.

Inhibition of UBA6 by inosine augments tumour immunogenicity and responses.

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity.

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome.

Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-β-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)-induced colitis model.

Cell graph neural networks enable the precise prediction of patient survival in gastric cancer.

Gastric cancer is one of the deadliest cancers worldwide. An accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients.

ATF3 Positively Regulates Antibacterial Immunity by Modulating Macrophage Killing and Migration Functions.

The clinical severity of () respiratory infection correlates with antibacterial gene signature. infection induces the expression of an antibacterial gene, as well as a central stress response gene, thus activating transcription factor 3 (ATF3). ATF3-deficient mice have attenuated protection against lethal pneumonia and have a higher bacterial load.

Targeting Proliferating Tumor-Infiltrating Macrophages Facilitates Spatial Redistribution of CD8 T Cells in Pancreatic Cancer.

Tumor-associated macrophages (TAMs) play crucial roles in cancer progression, but the contributions and regulation of different macrophage subpopulations remain unclear. Here, we report a high level of TAM infiltration in human and mouse pancreatic ductal adenocarcinoma (PDAC) models and that the targeting of proliferating F4/80+ macrophages facilitated cytotoxic CD8+ T-cell-dependent antitumor immune responses. A well-defined KPC-derived PDAC cell line and the murine Panc02 PDAC cell line were used.

Pan-Cancer Analysis and Validation Reveals that D-Dimer-Related Genes are Prognostic and Downregulate CD8 T Cells TGF-Beta Signaling in Gastric Cancer.

Cancer is considered one of the most lethal diseases worldwide. Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. As one of the most reproducible predictors of thromboembolism, the D-dimer level is commonly considered by oncologists.

Complete loss of miR-200 family induces EMT associated cellular senescence in gastric cancer.

The EMT (epithelial-to-mesenchymal-transition) subtype of gastric cancer (GC) is associated with poor treatment responses and unfavorable clinical outcomes. Despite the broad physiological roles of the micro-RNA (miR)-200 family, they largely serve to maintain the overall epithelial phenotype. However, during late-stage gastric tumorigenesis, members of the miR-200 family are markedly suppressed, resulting in the transition to the mesenchymal state and the acquisition of invasive properties.

Genome-scale CRISPR-Cas9 screen of Wnt/β-catenin signaling identifies therapeutic targets for colorectal cancer.

Aberrant activation of Wnt/β-catenin pathway is a key driver of colorectal cancer (CRC) growth and of great therapeutic importance. In this study, we performed comprehensive CRISPR screens to interrogate the regulatory network of Wnt/β-catenin signaling in CRC cells. We found marked discrepancies between the artificial TOP reporter activity and β-catenin-mediated endogenous transcription and redundant roles of T cell factor/lymphoid enhancer factor transcription factors in transducing β-catenin signaling.

Overexpression of PLXDC2 in Stromal Cell-Associated M2 Macrophages Is Related to EMT and the Progression of Gastric Cancer.

The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database.

CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer.

Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts.

Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer.

Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients.

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment.

The immunosuppressive status of the tumor microenvironment (TME) remains poorly defined due to a lack of understanding regarding the function of tumor-associated macrophages (TAMs), which are abundant in the TME. TAMs are crucial drivers of tumor progression, metastasis, and resistance to therapy. Intra- and inter-tumoral spatial heterogeneities are potential keys to understanding the relationships between subpopulations of TAMs and their functions.

MAP30 protein from Momordica charantia is therapeutic and has synergic activity with cisplatin against ovarian cancer in vivo by altering metabolism and inducing ferroptosis.

Increasing evidence shows that Traditional Chinese Medicine (TCM) has an obvious appeal for cancer treatment, but there is still a lack of scientific investigation of its underlying molecular mechanisms. Bitter melon or bitter gourd (Momordica charantia) is an edible fruit that is commonly consumed, and it is used to cure different diseases in various ancient folk medical practices. We report that a bioactive protein, MAP30, isolated from bitter melon seeds exhibited potent anticancer and anti-chemoresistant effects on ovarian cancer cells.