FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I–III

作者：Minlin Jiang, Chunyan Wu, Liping Zhang, Chenglong Sun, Hao Wang, Yi Xu, Hui Sun, Jun Zhu, Wencheng Zhao, Qiyu Fang, Jia Yu, Peixin Chen, Shengyu Wu, Zixuan Zheng, Yayi He, Caicun Zhou · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2021-002339 · 被引用次数：29 · 研究领域：Lung Cancer Research Studies、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Background Immunotherapies may prolong the survival of patients with small-cell lung cancer (SCLC) to some extent. The role of forkhead box protein P3 (FOXP3) in tumor microenvironment (TME) remains controversial. We aimed to examine FOXP3-related expression characteristics and prognostic values and to develop a clinically relevant predictive system for SCLC. Methods We enrolled 102 patients with histologically confirmed SCLC at stages I–III. Through immunohistochemistry, we determined the expression pattern of FOXP3 and its association with other immune biomarkers. By machine learning and statistical analysis, we constructed effective immune risk score models. Furthermore, we examined FOXP3-related enrichment pathways and TME traits in distinct cohorts. Results In SCLC, FOXP3 level was significantly associated with status of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), CD4, CD8, and CD3 (p=0.002, p=0.001, p=0.002, p=0.030, and p<0.001). High FOXP3 expression showed longer relapse-free survival (RFS) than the low-level group (41.200 months, 95% CI 26.937 to 55.463, vs 14.000 months, 95% CI 8.133 to 19.867; p=0.008). For tumor-infiltrating lymphocytes (TILs), subgroup analysis demonstrated FOXP3 and PD-1, PD-L1, lymphocyte activation gene-3, CD3, CD4, or CD8 double positive were significantly correlated with longer RFS. We further performed importance evaluation for immune biomarkers, constructed an immune risk score incorporating the top three...