Inhibition of integrin αvβ6 sparks T-cell antitumor response and enhances immune checkpoint blockade therapy in colorectal cancer.

Background: Integrin αvβ6 is a heterodimeric cell surface protein whose cellular expression is determined by the availability of the integrin β6 subunit (ITGB6). It is expressed at very low levels in most organs during tissue homeostasis but shows highly upregulated expression during the process of tumorigenesis in many cancers of epithelial origin. Notably, enhanced expression of integrin αvβ6 is associated with aggressive disease and poor prognosis in numerous carcinoma entities.

Commensal Clostridiales strains mediate effective anti-cancer immune response against solid tumors.

Despite overall success, T cell checkpoint inhibitors for cancer treatment are still only efficient in a minority of patients. Recently, intestinal microbiota was found to critically modulate anti-cancer immunity and therapy response. Here, we identify Clostridiales members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC).

Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set out to investigate the functional role of PTPN2 in the pathogenesis of human colorectal carcinoma (CRC), as its role in immune-silent solid tumors is poorly understood. We demonstrate that in human CRC, increased PTPN2 expression and activity correlated with disease progression and decreased immune responses in tumor tissues.

A quick flow cytometry protocol to assess Helicobacter pylori viability.

Here we present an easy flow cytometry protocol to study the viability of Helicobacter pylori which also enables the detection of even low live bacteria densities. This protocol has potential utility for a fast and accurate assessment of experimental eradication methods against H. pylori.

Loss of PTPN23 Promotes Proliferation and Epithelial-to-Mesenchymal Transition in Human Intestinal Cancer Cells.

Background/objectives: Protein tyrosine phosphatase nonreceptor type 23 (PTPN23) has recently been associated with several human epithelial cancers via regulation of growth factor signaling. Colorectal carcinoma (CRC) is a leading cause for cancer-related death worldwide and is associated with aberrant epidermal (EGF) and vascular endothelial growth factor signaling. Here, we investigated whether PTPN23 might play a role in CRC.

Intestinal microbiota and colorectal carcinoma: Implications for pathogenesis, diagnosis, and therapy.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and leading cause of cancer-related deaths worldwide. In recent years, there has been a growing realisation that lifestyle plays a major role for CRC development and that intestinal microbiota, which are shaped by lifestyle and nutrition habits, may be critically involved in the pathogenesis of CRC. Although the precise mechanisms for how the microbiota contribute to CRC development and progression remain elusive, increasing evidence suggests a direct causative role for the intestinal microbiota in modulating signalling pathways, anti-tumour immune responses and cell proliferation.

Deletion of Protein Tyrosine Phosphatase Nonreceptor Type 2 in Intestinal Epithelial Cells Results in Upregulation of the Related Phosphatase Protein Tyrosine Phosphatase Nonreceptor Type 23.

Background/aims: Knockdown of protein tyrosine phosphatase nonreceptor type 2 () exaggerates IFN-γ-induced intestinal barrier defects, but mice constitutively lacking in epithelial cells (PTPN2xVilCre mice) do not show changes in epithelial function or enhanced susceptibility to experimental colitis. Here, we investigated whether PTPN2 modulates the expression of related tyrosine phosphatases.

Methods: PTPN2 knockdown in HT-29 cells was induced using siRNA constructs.

Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis.

Objectives: Esophageal microbiota and regulation of adaptive immunity are increasingly being investigated in eosinophilic esophagitis (EoE). Toll-like receptors (TLRs) play a central role in the initiation and maintenance of innate immune activity. Our objective was to characterize the esophageal and duodenal innate immune response in EoE and its modulation by dietary therapy.

Propionibacterium acnes overabundance and natural killer group 2 member D system activation in corpus-dominant lymphocytic gastritis.

Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8 T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H.

TRPV4-Mediated Detection of Hyposmotic Stress by Skin Keratinocytes Activates Developmental Immunity.

As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos. Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms.

Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates.

All animals develop in association with complex microbial communities. It is now well established that commensal microbiota is essential for the correct functionality of each organ in the host. Particularly, the commensal gastro-intestinal microbiota (CGIM) is a key factor for development, immunity and nutrient conversion, rendering them bio-available for various uses.