Liver disease stage determines whether the immune response stifles or stimulates tumor growth

CT scan showing liver tumors in a patient with hepatocellular carcinoma (HCC)

Researchers at the Center for Cancer Research and colleagues from three cancer research centers in Germany have discovered a mechanism whereby precancerous liver cells, found in individuals with chronic liver disease, can prevent neighboring cells from becoming cancerous but can also speed the growth of cells that have already become cancerous.

Previous research on the development of hepatocellular carcinoma (HCC), the most common form of liver cancer and the second most common cause of cancer-related deaths worldwide, has shown that precancerous liver cells normally release a cytokine called CCL2, triggering an immune response. The body’s macrophages, a type of white blood cell that engulfs and digests cancer cells, then rush to the scene and clear away the precancerous cells, effectively halting their transformation into malignant cells.

But according to the new study, published October 10 in Cancer Cell, the same immune response can have the opposite effect on tumor cells that have already become established in the liver. In this case, CCL2 released by precancerous cells stimulates more rapid growth of HCC tumors. In other words, the immune response that normally prevents initiation of HCC may also promote progression of established HCC.

The findings highlight the importance of closely tracking the progression of chronic liver disease to determine whether to use a treatment that could have drastically opposite effects depending on the stage of disease. In patients with HCC tumors, drugs that block the immune response triggered by the CCL2 cytokine can slow HCC tumor growth. However, in patients with only precancerous cells, the same drugs could interrupt an important immune system function that destroys the cells before they transition into HCC tumors.

Summary Posted: Sat, 10/01/2016