Immunotherapy: Arming the body against liver cancer
STIMULATING the immune system against the development of tumor cells could be a useful strategy to delay or prevent the onset of liver cancer in chronic hepatitis B patients, according to a recent A*STAR-funded study1. Writing in Gastroenterology, researchers from the Singapore Institute for Clinical Research and other institutes based in Singapore describe their discovery that most patients, even those whose infection has progressed to cancer, have immune T cells that respond to tumor cells. While this could be used to bolster resistance to the development of new tumors, T-cell exhaustion inhibited the response in those who already have liver cancer, the researchers found.
Chronic infection with hepatitis B virus (Fig. 1) is a significant risk factor for the development of the liver cancer known as hepatocellular carcinoma (HCC). Over time, chronic infection typically leads to liver cirrhosis, which develops into HCC in about 80% of patients. This is of particular concern in parts of Asia where hepatitis B virus infection rates are greater than 1 in 10.
There has been limited success in treating HCC using chemotherapy, and removal of the damaged parts of the liver is usually not viable. This leaves only full transplantation as a treatment option. Researchers from A*STAR, the National University of Singapore and Gleneagles Hospital, led by Antonio Bertoletti, studied the possibility of immunotherapy-turning the body's immune system against the tumor cells.
The researchers tested the response of HLA-A2-a type of T cell widespread in Asian and Caucasian populations-to tumor antigens and hepatitis B virus proteins. The T cells were from 30 hepatitis B-infected patients, 10 of whom also had cirrhosis while another 10 had HCC.
T cells from most patients responded to tumor antigens, and some to more than one type of antigen, whereas very few patients responded to the viral proteins. The most active tumor antigens were able to stimulate a full-blown immune reaction. In the cancer patients, however, there was evidence of T-cell exhaustion.
In the livers and tumors of the HCC patients, the researchers observed higher than normal levels of T cells associated with programmed cell death, leading to the speculation that their presence could promote T-cell exhaustion. Blocking active proteins associated with programmed death could perhaps rescue T-cell function, the researchers suggest.
Having demonstrated that T cells can be stimulated to respond against tumor cells in patients with cirrhosis, the researchers believe that in the future it may be possible to target tumor cells in a prophylactic manner to prevent or delay progression to HCC.
- Gehring, A.J., Ho, Z.Z., Tan, A.T., Aung, M.O., Lee, K.H., Tan, K.C., Lim, S.G., Bertoletti, A. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology published online 27 April 2009 (doi: 10.1053/j.gastro.2009.04.045).