Factors associated with immune‑related severe adverse events (Review)

Immune checkpoint inhibitors (ICIs) are frequently used in cancer treatment. Despite their clinical benefits, they can also cause a wide range of immune-related adverse events (ir-AEs). The overall incidence of irAEs in cancer patients treated with immunotherapy ranges from 70-90%, while that of immune-related severe adverse events (ir-SAEs) is 10-43%. ir-SAEs pose a significant risk to patient safety as they are extremely frequent and lethal. Due to non-specific manifestations, rapid progression and significant morbidity, it is essential to identify factors associated with ir-SAEs early to predict high-risk groups for treatment safety. However, less information is available on the factors causing ir-SAEs, and further research is needed. The present study reviews the factors associated with ir-SAEs in terms of demographic characteristics, disease-related information and laboratory examinations to provide a clinical reference. In terms of demographic characteristics, age, body mass index, smoking, ethnicity and cancer family history may influence the incidence of ir-SAEs. Regarding disease-related information, the risks factors associated with ir-SAEs may include disease history, treatment regimen and cancer type. For laboratory examinations, risk factors associated with ir-SAEs include the laboratory examination parameters of peripheral blood cells, immunocytes, cytokines/chemokines, genetics, gut microbia, proteins and brain injury markers. All of these risk factors can stimulate the body's inflammatory response, leading to over proliferation of T cells and other inflammatory factors. In addition, the use of ICIs may disrupt gut microbial homeostasis and dysregulate the pre-existing intestinal ecology, which may therefore trigger inflammatory signaling pathways, affect overall immune function and increase the occurrence of ir-SAEs. In response to the aforementioned risk factors, it is recommended that medical professionals incorporate their analysis into routine patient testing for early identification of patient ir-SAEs and to create early individualized interventions to improve the safety for immunotherapy patients.