Research progress on predictive markers of immunological adverse events induced by immune checkpoint inhibitors in the treatment of malignant tumors
Objective To review studies on predictive biomarkers for immune-related adverse events(irAEs)caused by im-mune checkpoint inhibitors(ICIs)in the treatment of malignant tumors and enhance the ability of early identification and treatment of irAEs,thereby optimizing the therapeutic efficacy of ICIs.Methods Using"immune checkpoint inhibitor,immunotherapy,tumor/cancer/oncology/neoplasm/carcinoma,adverse event/toxicity,and biomarker"as keywords,re-lated literature was searched in PubMed,Wanfang Data and CNKI databases for from January 1,2018,to October 31,2023.A total of 184 relevant articles were retrieved.Inclusion criteria focused on literature related to biological markers for predicting irAEs caused by ICIs.Exclusion criteria included review articles and conference papers.Finally,62 articles were included based on the inclusion and exclusion criteria.Results irAEs involve multiple organs throughout the body,commonly including skin-related diseases and colitis,while less common ones include hepatitis,pneumonia,myocarditis,endocrine system,nervous system,and rheumatic immune system diseases.Currently,commonly used predictive markers have their own advantages and disadvantages,and the specificity of most predictive markers is not high.Antibodies a-gainst tuberculosis and anti-mitochondrial antibodies may help predict liver injury induced by ICIs,while serum levels of sCD163,CXCL5,and bullous pemphigoid(BP)180 IgG can effectively predict the occurrence of skin-related irAEs.Ele-vated levels of IL-17,neutrophils,eosinophils,and white blood cells can predict the occurrence of colitis induced by ICIs.Eosinophil counts＞240/μL and relative eosinophil counts＞3.2％are significantly associated with the incidence of endo-crine irAEs.Peripheral blood markers,gut microbiota,and emerging markers such as immune cells,cytokines,and au-toantibodies have rarely been reported in clinical settings,but they have a promising future and are expected to predict irAEs together with other markers.Conclusion Relying on a single biomarker is difficult to accurately predict the occur-rence of specific irAEs.In the future,interdisciplinary collaboration should be strengthened for larger-scale,deeper re-search.Moreover,the combined use of multiple biomarkers in clinical practice may more effectively predict the occurrence of irAEs,thus improving clinicians'ability to early identify and timely treat serious adverse reactions related to ICIs.
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