Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis

Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II−) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine

Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis

Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine

Multicenter Analysis of Gestational Trophoblastic Neoplasia in Turkey

WOS: 000338633500049PubMed ID: 24870768Background: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. Materials and Methods: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. Results: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. Conclusions: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN