CSC Cell Proliferation work with Helmholtz University
Scientists investigating the development of liver cancer have discovered a healthy immune-system ‘surveillance mechanism’ that keeps pre-cancerous cells under strict supervision, then removes them from the body in a timely manner.
Professor Lars Zender of the Helmholtz Centre for Infection Research in Braunschweig, Germany has an interest in liver cell carcinoma – the most common type of malignant cancer worldwide. Together with collaborators at several institutes in Germany and here at the Clinical Sciences Centre, he has shown that cells shocked into a state of suspended animation by signals sent out by their cancerous neighbours are then closely monitored by ‘T’ helper immune cells [cells that assist in immunological processes]. The suspended animation state called senescence is something that eventually happens to all cells after they have gone through 50 replications, but it can be brought on earlier with a shock from neighbouring cancer cells. Senescence slows down the growth of cancers: “the body prevents senescent cells from further changing and growing into a cancer,” explains Professor Zender. “We could see the immune system launches a strong reaction against these cells…it then removes them from the body after a couple of weeks”.
The researchers identified the surveillance mechanism in mice engineered to have deficient T helper immune cells. Senescent liver cells in these mice grew into a cancer, while the surveillance mechanism in mice with fully-functioning T cells removed the senescent cells before cancer could develop.
Jesus Gil, who heads the Cell Proliferation group at the CSC and was a contributor to the study, said: “This work by the Zender group is an amazing breakthrough that help us understand how the immune system cooperates with senescence for tumour suppression. Currently we are engaged with Lars in finishing additional experiments to find out which molecules senescent cells use to signal not only to the immune system, but also other cells in the lesions and tumour microenvironment to keep them from dividing.”
This newly-identified mechanism also indicates that HIV-positive patients are also at greater risk of liver cancer. The researchers followed this up by measuring the number of senescent cells in the livers of hepatitis C patients who were HIV-positive, and compared these with hepatatis C patients who didn’t have HIV. The first group showed an increase in senescent cells, because their bodies’ T cells have impaired function and cannot remove the senescent cells effectively. The second group didn’t, however.
“This clearly shows how important T cells are in the immune system’s monitoring of senescent cells,” commented Zender.
This work appears in Nature
Kang, T.-W., Yevsa, T., Woller, N., Hoenicke, L., Wuestefeld, T., Dauch, D., Hohmeyer, A., Gereke, M., Rudalska, R., Potapova, A., Iken, M., Vucur, M., Weiss, S., Heikenwalder, M., Khan, S., Gil, J., Bruder, D., Manns, M., Schirmacher, P., Tacke, F., Ott, M., Luedde, T., Longerich, T., Kubicka, S., Zender, L. (2011). Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature advance online publication.