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Unprecedented advances have been made in immune checkpoint inhibitors (ICIs) in the treatment of cancer. However, the overall benefits from ICIs are impaired by the increasing incidence of immune-related adverse events (irAEs). Although several factors and mechanisms have been proposed in the development of irAEs, there is still incomprehensive understanding of irAEs. Therefore, it is urgent to identify certain risk factors and biomarkers that predict the development of irAEs, as well as to understand the underlying mechanisms of these adverse events. Herein, we comprehensively summarize the state-of-the-art knowledge about clinical features and the related risk factors of irAEs. Particularly, we also discuss relevant mechanisms of irAEs and address the mechanism-based strategies, aiming to develop a tailored management approach for irAEs.

To discover phytochemicals as lead compounds for cancer treatment, cratoxylumxanthone C, a natural xanthone, was obtained from Cratoxylum cochinchinense (Lour.) Bl., for which there have been no reports on the biological effects against cancer. Our study revealed that cratoxylumxanthone C had significant anti-tumor activity by inducing apoptosis, augmenting cellular reactive oxygen species (ROS), and arresting cell circle. The mechanistic examination showed the inhibition of A549 cell proliferation and metastasis by cratoxylumxanthone C was coupled with the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) signaling pathways. Furthermore, the zebrafish models confirmed its significant in vivo anti-tumor activity, in which cratoxylumxanthone C inhibited tumor proliferation and metastasis and suppressed the angiogenesis. Comprehensively, these cellular and zebrafish experiments implied that cratoxylumxanthone C may have the potential to become an anti-tumor agent for lung cancer, especially non-small cell lung cancer (NSCLC).

It is of great clinical value to investigate the immune-related adverse events (irAEs), especially demyelinating lesions, caused by immune checkpoint inhibitors (ICIs). The incidence of demyelinating lesions is less frequent in irAEs, but once it occurs, it will seriously affect the survival of patients. The present study reports a case of durvalumab-induced demyelinating lesions in a patient with extensive-stage small-cell lung cancer. Subsequently, the patient receives a high intravenous dose of methylprednisolone and his condition is improved after 21 days of treatment. Altogether, early diagnosis and treatment of ICIs-related neurological irAEs is of great significance to the outcome of the patient’s condition.

Drug-induced liver injury (DILI) has become one of the major challenges of drug safety all over the word. So far, about 1,100 commonly used drugs including the medications used regularly, herbal and/or dietary supplements, have been reported to induce liver injury. Moreover, DILI is the main cause of the interruption of new drugs development and drugs withdrawn from the pharmaceutical market. Acute DILI may evolve into chronic DILI or even worse, commonly lead to life-threatening acute liver failure in Western countries. It is generally considered to have a close relationship to genetic factors, environmental risk factors, and host immunity, through the drug itself or its metabolites, leading to a series of cellular events, such as haptenization and immune response activation. Despite many researches on DILI, the specific biomarkers about it are not applicable to clinical diagnosis, which still relies on the exclusion of other causes of liver disease in clinical practice as before. Additionally, circumstantial evidence has suggested that DILI is mediated by the immune system. Here, we review the underlying mechanisms of the immune response to DILI and provide guidance for the future development of biomarkers for the early detection, prediction, and diagnosis of DILI.