Cancer Immunoprevention: Challenges and Potential Opportunities for Use of Immune Checkpoint Inhibitors.

Cancer immunoprevention is achieved through promoting antitumor immune surveillance to block tumor formation and progression. Following the success of prophylactic vaccines against human papillomavirus (HPV) in preventing HPV-associated cancer, immunopreventive cancer vaccines targeting tumor antigens have been increasingly evaluated against cancers of noninfectious origin. While advances in cancer immunotherapy with immune checkpoint inhibitors (ICI) have clearly shown that the host immune system can mount effective antitumor immunity against tumor antigens when immune checkpoints are optimally blocked, the use of ICIs in the prevention setting has not been widely explored because of concerns of ICI-associated adverse events. In this issue of Cancer Prevention Research, Chung and colleagues demonstrate that the human cirrhotic liver harbors neoantigens, which accumulate further as the disease progresses to hepatocellular carcinoma (HCC), suggesting that cirrhotic liver may be susceptible to ICI therapy. Utilizing an established mouse model of carcinogen-induced liver fibrosis and HCC, they show that intermittent intervention by ICI, anti-mouse PD-1 (CD279) antibody, can prevent the progression of the precancerous stage of cirrhosis to HCC accompanied by increased T-cell infiltrates in the liver parenchyma. Importantly, there were no overt ICI-associated toxicities in the treated mice, indicating that safe dosing regimens could be established. This work is both significant and timely, opening the door to future studies, where the utility of ICI therapy can be further investigated not only in cirrhosis but other high-risk precancerous conditions. In this perspective, we discuss the implications of their findings, and the challenges and potential opportunities for use of ICIs for cancer immunoprevention.See related article by Chung et al., p. 911. ©2020 American Association for Cancer Research.