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 study.
Writing in Gastroenterology, researchers from the Singapore Institute for Clinical Sciences and other institutes based in Singapore describe their discovery that most patients, even those whose infection has progressed to cancer, have T cells that respond to tumor cells (Fig. 1). While this could be used to bolster resistance to the development of new tumors, T-cell exhaustion inhibited the response in those who already had liver cancer, the researchers found.
Chronic infection with hepatitis B virus is a significant risk factor for the development of 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 using immunotherapy—turning the body’s immune system against the tumor cells.
The researchers tested the response presented by HLA-A2—a type of human leukocyte antigen (HLA) widespread in Asian and Caucasian populations—to tumor antigens and hepatitis B virus proteins. T cells were tested from 30 hepatitis B-infected patients, 10 of whom also had cirrhosis while another 10 had HCC.
Most HCC patients responded to tumor antigens, and some to more than one type of antigen, whereas very few patients responded to viral proteins. However, there was evidence of T-cell exhaustion, and in the liver and tumors of the HCC patients, the researchers observed higher levels of the programmed death 1 (PD-1) receptor on T cells. The results indicate that blocking PD-1 — a receptor associated with functional exhaustion — could perhaps rescue T-cell function. In contrast, the most active tumor antigens in patients without HCC (chronic hepatitis B or cirrhosis patients) were able to stimulate a multifunctional T-cell response.
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.