Featured
-
-
Article
| Open Access
Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis
Given the association of gut microbiota dysbiosis with hypertriglyceridemic pancreatitis (HTGP), authors assess the gut microbial diversity of patients with HTGP, and provide immunological insight utilising a murine model.
- Guanqun Li
- , Liwei Liu
- & Bei Sun
-
Article
| Open Access
Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors
Tumor stroma is a key component of the immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). Here, in preclinical PDAC models, the authors show that depletion of FAP-expressing cancer associated fibroblasts with FAP-targeted CAR T cells results in a loss of the integrity of the desmoplastic matrix, rendering tumors more susceptible to sequential treatment with mesothelin-targeted CAR-T cells.
- Zebin Xiao
- , Leslie Todd
- & Ellen Puré
-
Article
| Open Access
NFIC regulates ribosomal biology and ER stress in pancreatic acinar cells and restrains PDAC initiation
Pancreatic acinar differentiation can be tumour suppressive for pancreatic ductal adenocarcinoma (PDAC). Here the authors identify nuclear factor I family of transcription factors NFIC as a regulator of pancreatic acinar cell function that restrains mutant KRas-driven pancreas cancer initiation in mice.
- Isidoro Cobo
- , Sumit Paliwal
- & Francisco X. Real
-
Article
| Open Access
In mouse chronic pancreatitis CD25+FOXP3+ regulatory T cells control pancreatic fibrosis by suppression of the type 2 immune response
The function of T regulatory cells in the tissue fibrosis in chronic pancreatitis is not fully understood. Here the authors use a mouse model of chronic pancreatitis to show that Treg cells reduce IL-4 mediated chronic inflammation in the pancreas associated with M2-like macrophages in vivo.
- Juliane Glaubitz
- , Anika Wilden
- & Matthias Sendler
-
Article
| Open Access
Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer
All-trans retinoic acid - ATRA- is known to remodulate the stroma of pancreatic cancer in mice. Here, the authors carried out a Phase Ib trial in pancreatic patients and show that ATRA in combination with chemotherapy is a safe potential treatment for patients with advanced pancreatic cancer, and demonstrate a stromal modulatory effect.
- Hemant M. Kocher
- , Bristi Basu
- & David J. Propper
-
Article
| Open Access
Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy
Immune checkpoint inhibitors have limited efficacy in tumors with lower mutational burden and non-permissive microenvironment. Here, the authors show that combining MEK inhibition with an agonist anti-CD40 immunostimulatory antibody improves antitumor treatment by inducing immunogenic changes in the tumor microenvironment.
- Daniel Baumann
- , Tanja Hägele
- & Rienk Offringa
-
Article
| Open Access
A preclinical model of chronic pancreatitis driven by trypsinogen autoactivation
Inflammatory diseases of the pancreas are currently untreatable and lack a pre-clinical model that recapitulates the hallmarks of the human pathology. Here, the authors generate a knock-in mouse strain with increased tripsinogen autoactivation and show that it develops spontaneous pancreatic pathology with some key features of human pancreatitis.
- Andrea Geisz
- & Miklós Sahin-Tóth
-
Article
| Open Access
Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis
Pancreatitis often develops as a consequence of ductal obstruction. Here, the authors show that bicarbonate ions initiate the release of neutrophil extracellular traps (NETs) that form pancreatic ductal aggregates and occlude the ducts, thereby driving pancreatitis in mice and humans.
- Moritz Leppkes
- , Christian Maueröder
- & Christoph Becker
-
Article |
The oncogenic microRNA miR-21 promotes regulated necrosis in mice
The microRNA miR-21 is overexpressed in cancer and is thought to function through anti-apoptotic activity. Here, Ma et al. show that deleting or blocking miR-21 in mice protects against acute pancreatitis and TNF-α-induced tissue damage by inhibiting RIP3-dependent regulated necrosis (necroptosis).
- Xiaodong Ma
- , Daniel J. Conklin
- & Yong Li
-
Article |
Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis
Chronic pancreatitis is an inflammatory disease accompanied by fibrosis. Here the authors show that pancreatic stellate cells produce IL-4 and IL-13 that trigger alternative activation of macrophages, and that genetic or pharmacological inhibition of IL-4/IL-13 signaling ameliorates the disease.
- Jing Xue
- , Vishal Sharma
- & Aida Habtezion
-
Article
| Open Access
Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR
Patients with cystic fibrosis harbour mutations in the CFTR chloride channel and often develop diabetes for reasons that are poorly understood. Here Guo et al.show that CFTR is involved in the regulation of glucose-stimulated insulin secretion from pancreatic β-cells.
- Jing Hui Guo
- , Hui Chen
- & Hsiao Chang Chan
CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes