Abstract
BackgroundThe early diagnosis of hepatocellular carcinoma (HCC) can greatly improve patients’ 5-year survival rate, and the early efficacy assessment is important for oncologists to harness the anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced HCC. The lack of effective predicting biomarkers not only leads to delayed detection of the disease but also results in ineffective immunotherapy and limited clinical survival benefit.MethodsWe exploited the single-cell approach (cytometry by time of flight (CyTOF)) to analyze peripheral blood mononuclear cells from multicohorts of human samples. Immune signatures for different stages of patients with HCC were systematically profiled and statistically compared. Furthermore, the dynamic changes of peripheral immune compositions for both first-line and second-line patients with HCC after anti-PD-1 monotherapy were also evaluated and systematically compared.ResultsWe identified stage-specific immune signatures for HCC and constructed a logistic AdaBoost-SVM classifier based on these signatures. The classifier provided superior performance in predicting early-stage HCC over the commonly used serum alpha-fetoprotein level. We also revealed the treatment stage-specific immune signatures from peripheral blood and their dynamical changing patterns, all of which were integrated to achieve early discrimination of patients with non-durable benefit for both first-line and second-line anti-PD-1 monotherapies.ConclusionsOur newly identified single-cell peripheral immune signatures provide promising non-invasive biomarkers for early detection of HCC and early assessment for anti-PD-1 immunotherapy efficacy in patients with advanced HCC. These new findings can potentially facilitate early diagnosis and novel immunotherapy for patients with HCC in future practice and further guide the utility of CyTOF in clinical translation of cancer research.Trial registration numbersNCT02576509 and NCT02989922.
Funder
National Major Scientific and Technological Special Project for Significant New Drugs Development during the Thirteenth Five-year Plan Period
Natural Basic Research Program of China
Natural Science Foundation of Zhejiang Province
Subject
Cancer Research,Pharmacology,Oncology,Molecular Medicine,Immunology,Immunology and Allergy
Cited by
18 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献