Immune response to gut microbes may provide powerful weapon to fight against cancer

The bodys immune system is activated by gut microbes after cancer cells invade the intestine becoming a catalyst for triggering defenses against cancer cells researchers reported April 12 in the journal Nature.

The discovery — the first to show tumor-stimulation effects in inflammatory bowel disease or IBD — indicates a promising new space for the development of cancer immunotherapies or cancer-fighting immunotherapies that harness the immune systems of cancer patients to promote bone marrow regeneration and restore immune function.

We discovered a novel immunological process (…) which enabled us to activate one cell of the immune system called adaptive immunity to characterize how myeloid and T-cell survival is regulated throughout the intestine said the studys lead author Brinda Karan of York University Canada. This commentary helps us take this new knowledge further.

The Nature article describes a new mechanism by which myeloid and T-cell survival is regulated through gut microbiota. Over thousands of years the microbial diversity of the gut has evolved to create a functioning immune system to protect against and eliminate invading microbes whereas T-cells are thought to be more genetically conserved to maintain a healthy intestinal system.

The genetic diversity of healthy myelin tissue is maintained within the intestine through a normal process called translocation a process whereby an invading microbe crosses the epithelial surface of the host and induces myeloid survival in comparison to T-cells which are recruited to the intestinal epithelium following injury. Translocation also allows the initiation of interaction or migration of the myeloid and T-cell populations to colonize the intestine per se from a cancer cell.

Using flexible liposomes or flexible membranes that provide a cohesive profile on the inside Karan and her colleagues used the platform to characterize the survival of a colony of Lactobacillus due to T-cell recruitment to the intestinal epithelium at only two weeks after tumor invasiveness. The authors observed that a specific strain of L. rettgerii bacteria which is known to promote intestinal health in animals was able to induce myeloid survival for 5 weeks after tumor invasion.

Several experiments suggested that myeloid survival in the early stages of cancer was somehow dependent on the ability of the invasive microbial cells to combat cancer cells via a cell engulfing system called endothelial cell engulfment. The authors demonstrated that this system is of relevance for myeloid survival in the early stages of cancer adding that the placement of endothelial cells and the specific gene expression of endothelial cells in close proximity to pro-tumor cells may be important factors that influence the survival of myeloid cells.

Through the application of Toll-like receptor agonist therapy the authors reported that cancer cells not only began to eat their lining when it was transplanted to the colon of mice but also that the cancer cells resulting in an in vivo myeloid survival for over 4 months generated pro-tumor CD4 T cells.

Our results indicate that myeloid lines can overcome unpredictable invasion by tumors and provide a reliable tool for the prevention and treatment of cancer Karan said.

Next-step in the study will be to validate this safety of the engineered myeloid lines in humans and to obtain early live studies of those who benefitted from the treatment.