Inhibition of insulin-like growth factors increases production of CXCL9/10 by macrophages and fibroblasts and facilitates CD8 cytotoxic T cell recruitment to pancreatic tumours.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with an urgent unmet clinical need for new therapies. Using a combination of assays and preclinical models we demonstrate that therapeutic inhibition of the IGF signalling axis promotes the accumulation of CD8 cytotoxic T cells within the tumour microenvironment of PDAC tumours. Mechanistically, we show that IGF blockade promotes macrophage and fibroblast production of the chemokines CXCL9 and CXCL10 to facilitate CD8 T cell recruitment and trafficking towards the PDAC tumour.

Mesothelin Secretion by Pancreatic Cancer Cells Co-opts Macrophages and Promotes Metastasis.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, yet effective treatments to inhibit PDAC metastasis are lacking. The rich PDAC tumor microenvironment plays a major role in disease progression. Macrophages are the most abundant immune cell population in PDAC tumors and can acquire a range of functions that either hinder or promote tumor growth and metastasis.

Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease and cytotoxic chemotherapy is the standard of care treatment for patients with advanced disease. Here, we investigate how the microenvironment in PDAC liver metastases reacts to chemotherapy and its role in metastatic disease progression post-treatment, an area which is poorly understood.

Design: The impact of chemotherapy on metastatic disease progression and immune cell infiltrates was characterised using flow and mass cytometry combined with transcriptional and histopathological analysis in experimental PDAC liver metastases mouse models.

Bile acid malabsoption: a forgotten diagnosis?

Bile acid malabsorption (BAM) is never life threatening but can cause chronic symptoms. A survey of senior British gastroenterologists was conducted to examine their approach to patients with potential BAM. Of the 706 gastroenterologists contacted, 62% replied.