Immunobiology of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a tumor of increasing incidence and high mortality worldwide. Diagnosis of HCC is often difficult, especially at early stages of disease. Additionally, current treatment options are limited. HCC usually develops in an environment of chronic liver disease. The immune system has an important role in shaping this environment, especially in chronic viral hepatitis, the leading cause of HCC. However, the immune system also plays a role in natural immunity against HCC although this is apparently not sufficient to control the majority of tumors. This failure in tumor control is due to multiple immunomodulatory mechanisms employed by HCC to subvert the immune system. In this review, we will summarize the current knowledge about the role of the immune system in hepatocarcinogenesis. Additionally, we will describe the mechanisms used by the immune system to control established lesions and the reasons why these immune responses apparently fail so often. Finally, possible implications for the design of novel immunotherapeutic strategies will be discussed.

Heterogeneity of liver cancer and personalized therapy

“…Immunotherapy strategies such as chimeric antigen receptor T cells and immune checkpoint blockade have been developed for decades in various human tumors, carrying high expectations based upon recent progress. As an "immune organ", liver shows unique antior pro-tumor responses during the progression of HCC [107]. Immune-modulators, tumor vaccines and adoptive immunotherapy proved effective in the clinical practice of HCC [108].…”

Immunobiology of Monocytes/Macrophages in Hepatocellular Carcinoma

“…In HCC, several lines of evidence have suggest a positive role of immune system, e.g., by controlling hepatoma growth [7,[27][28][29]. Indeed, data from clinical investigations have revealed that HCC patients with an increased intratumoral accumulation of cytotoxic CD8 + T lymphocytes had a superior 5-year survival rate and a prolonged recurrence-free survival after liver resection [11,30].…”

“…At present, several tumor-associated antigens (TAAs) of HCC have been identified, which has been recently introduced [7,33]. In brief, several shared tumor antigens could also be recognized as antigens targeted by cytotoxic CD8 + T cells in HCC, e.g., human telomerase-reverse transcriptase (hTERT) or NY-ESO-1.…”

“…HCC is usually present in inflamed fibrotic and/or cirrhotic liver with extensive leukocyte infiltration [6,7]. Thus, the immune status at different tumor sites can largely influence the biological behavior of HCC [6,8,9].…”

Immunotherapy for hepatocellular carcinoma: From basic research to clinical use

“…Immunotherapy has been explored in HCC for decades [4] and carries high expectations due to the recent progress in other malignancies such as melanoma. Different from other organs, liver shows its distinguished characteristics, such as an "immune organ", and patients with HCC present with unique anti-or pro-tumor responses during the development and progression of HCC [5] . Immunotherapy can be categorized into several types according to their distinct strategies.…”