Abstract
Immune checkpoint inhibitors represent one of the most significant recent advances in clinical oncology, since they dramatically improved the prognosis of deadly cancers such as melanomas and lung cancer. Treatment with these drugs may be complicated by the occurrence of clinically-relevant adverse drug reactions, most of which are immune-mediated, such as pneumonitis, colitis, endocrinopathies, nephritis, Stevens Johnson syndrome and toxic epidermal necrolysis. Drug-induced steatosis and steatohepatitis are not included among the typical forms of cancer immunotherapy-induced liver toxicity, which, instead, usually occurs as a panlobular hepatitis with prominent lymphocytic infiltrates. Nonetheless, non-alcoholic fatty liver disease is a risk factor for immunotherapy-induced hepatitis, and steatosis and steatohepatitis are frequently observed in this condition. In the present review we discuss how these pathology findings could be explained in the context of current models suggesting immune-mediated pathogenesis for steatohepatitis. We also review evidence suggesting that in patients with hepatocellular carcinoma, the presence of steatosis or steatohepatitis could predict a poor therapeutic response to these agents. How these findings could fit with immune-mediated mechanisms of these liver diseases will also be discussed.
Highlights
Cancer cells evade host immune responses by activating specific immune tolerance mechanisms, which include key proteins of the immune checkpoints physiologically involved in self-tolerance
By reviewing the literature about the relationship between non-alcoholic fatty liver disease (NAFLD), in its various forms, and cancer immunotherapy, we showed an intricate connection between the two (Figure 1)
Available data show that may steatosis and steatohepatitis be among the histopathological manifestations of immune checkpoint inhibitors (ICIs)-induced liver toxicity, but NAFLD might be a risk factor for the hepatotoxicity induced by these drugs
Summary
Cancer cells evade host immune responses by activating specific immune tolerance mechanisms, which include key proteins of the immune checkpoints physiologically involved in self-tolerance. These mechanisms consist of corepressor proteins on antigen presenting cells and their ligand receptors in T-lymphocytes, whose engagement reduces. By impairing these tolerance systems, anticancer agents of a new class, immune checkpoint inhibitors (ICIs), restore the immune response against tumors and induce clinical responses which are often impressive [1,2]. ICIs have revolutionized cancer therapy since their licensing, by dramatically improving the prognosis of patients with responsive tumors. Even though the usual presentation of ICI-induced hepatotoxicity is an immune-mediated hepatitis with hepatocellular damage and immune cell infiltration, sometimes the pathological features of cholangitis or a mixed pattern hepatitis with cholangitis are observed [11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
