Toxicity of Tumor Immune Checkpoint Inhibitors

More Attention Should Be Paid

Yu Liu; Hao Wang; Juan Deng; Chenglong Sun; Yayi He; Caicun Zhou


Transl Lung Cancer Res. 2019;8(6):1125-1133. 

In This Article

Abstract and Introduction


In recent years, immunotherapy, especially immune checkpoint inhibitors (ICIs), has achieved amazing results in the treatment of lung cancer, melanoma, renal clear cell carcinoma and other malignant tumors. Although ICIs have achieved significant efficacy in tumor treatment, the immune-related adverse events (irAEs) caused by non-specific immune activation of ICIs can directly affect the result of treatment, even threaten the life of patients. The most common form of irAEs involve the skin, lung, colon, liver and endocrine organs. However, it is noticeable that although irAEs of some organs are more common, actually any organ and tissue are likely to be affected, because of non-specific activation of the immune system. Other tissues and organs, though rare, can be more severe and even fatal, such as neurological disorders and myocarditis. Therefore, effective management of irAEs is of great importance for the efficacy of immunotherapy. This review is focused on the morbidity, clinical manifestations, diagnosis and treatment of tumor immune toxic effects.


Tumor immunotherapy can be grouped into two categories: active immunotherapy and passive immunotherapy. Active immunotherapy acts by stimulating and enhancing the host's antitumor immune response, which is also divided into specific and non-specific, the former using tumor-specific antigen, the latter using non-specific substances which can stimulate the immune system. Several ICIs have been used in cancer therapy (Table 1). Programmed death receptor-1/ligand-1 (PD-1/L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) checkpoint inhibitors are the most widely used. ICIs can activate non-specific immunity and cause irAEs. The pathophysiological mechanisms have not been fully elucidated, but are currently thought to be related to the invasion of normal tissue by immune cells. This paper mainly discusses the toxicities of ICIs in anti-tumors treatment.