IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis.

Expression of interleukin (IL)-17 family cytokines is associated with tumor-promoting inflammation. We found that low expression of IL17RA associated with worse prognosis in late-stage colorectal cancer (CRC) patients. Deletion of Il17ra in intestinal epithelial cells (IECs) in a murine model of CRC enhanced epithelial-to-mesenchymal transition (EMT) via increased expression of the epidermal growth factor receptor and subsequent activation of the kinase Src.

Report from the first Tanzania Liver Cancer Conference: a call for action to unite in the fight against liver cancer in Sub-Saharan Africa, 17-18 March 2023, Dar es Salaam, Tanzania.

The first Tanzania Liver Cancer Conference (TLCC2023) took place on 17-18 March 2023 in Dar es Salaam, Tanzania with the aim of raising awareness among healthcare providers on the problem that liver cancer poses to the Tanzanian population and the urgent need to address this important issue. The conference focused on the following agenda items: 1) to build awareness among local healthcare providers on the status of liver cancer in Tanzania and the available diagnostic and management options, 2) to update Tanzanian healthcare providers on the current standard of care for liver cancer provided in developed countries and recent advancements in liver cancer care and 3) to promote an inclusive and multidisciplinary approach in research and the clinical care of patients with liver cancer in Tanzania. TLCC2023 was preceded by community-facing pre-conference activities, including screening 684 community members for hepatitis B virus free of charge.

Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis.

In colorectal cancer patients, a high density of cytotoxic CD8 T cells in tumors is associated with better prognosis. Using a Stat3 loss-of-function approach in two wnt/β-catenin-dependent autochthonous models of sporadic intestinal tumorigenesis, we unravel a complex intracellular process in intestinal epithelial cells (IECs) that controls the induction of a CD8 T cell based adaptive immune response. Elevated mitophagy in IECs causes iron(II)-accumulation in epithelial lysosomes, in turn, triggering lysosomal membrane permeabilization.

Mesenchymal Cells in Colon Cancer.

Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer.

IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis.

Cancer-associated fibroblasts (CAFs) comprise one of the most important cell types in the tumor microenvironment. A proinflammatory NF-κB gene signature in CAFs has been suggested to promote tumorigenesis in models of pancreatic and mammary skin cancer. Using an autochthonous model of colitis-associated cancer (CAC) and sporadic cancer, we now provide evidence for a tumor-suppressive function of IKKβ/NF-κB in CAFs.

IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.

The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis.