Adverse and unconventional reactions related to immune checkpoint inhibitor therapy for cancer

Abstract

Immunotherapy is an emerging method for the treatment of cancer. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoint pathways and release the body's anti-tumor immunity. They consist mainly of antibodies against cytotoxic T lymphocyte associated antigen-4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death ligand 1 (PD-L1). Although ICI therapy has been shown to be effective at treating cancer, it can also destroy immune tolerance and lead to organ toxicity. These unwanted side effects are known as immune related adverse events (irAEs). ICI treatment can also cause unconventional reactions such as pseudoprogression and hyperprogression. Pseudoprogression looks like an increase in the tumor parenchyma but is actually a temporary inflammation in the tumor; hyperprogression refers to the acceleration of tumor growth after the start of immunotherapy. Understanding the mechanisms of these two phenomena and distinguishing their differences are necessary for the effective prevention and treatment of unconventional reactions.

Keywords: Hyperprogression; ICIs; Pseudoprogression; irAEs.