医学
CD8型
内科学
危险系数
肺癌
免疫衰老
CD28
肿瘤科
T细胞
肺炎
胃肠病学
队列
生物标志物
衰老
置信区间
肺
免疫学
免疫系统
生物化学
化学
作者
Kyung Hwan Kim,Hongryull Pyo,Hoyoung Lee,Dongryul Oh,Jae Myoung Noh,Yong Chan Ahn,Chang Gon Kim,Hong In Yoon,Jiyun Lee,Sehhoon Park,Hyun Ae Jung,Jong‐Mu Sun,Se‐Hoon Lee,Jin Seok Ahn,Keunchil Park,Bo Mi Ku,Eui–Cheol Shin,Myung‐Ju Ahn
标识
DOI:10.1016/j.ijrobp.2022.07.018
摘要
Associations between immunosenescence and radiation pneumonitis (RP) are largely unknown. We aimed to identify a peripheral blood T cell senescence biomarker to predict RP in patients with non-small cell lung cancer (NSCLC).Patients with locally advanced NSCLC who received definitive concurrent chemoradiotherapy (dCRT) were prospectively registered (cohort 1, n=23; cohort 2, n=31). Peripheral blood was collected at baseline, during dCRT, and at 1 month post-dCRT. Patients were dichotomized to grade ≥2 (G2+) RP and grade 0-1 (G0-1) RP. Flow cytometry was performed to assess phenotypes and functional properties of T cell subsets. RP incidence was estimated via competing risk analysis.Five and six patients exhibited G2+ RP following dCRT in cohorts 1 and 2, respectively. Patients with G2+ RP exhibited a more aged T cell pool and higher frequencies of senescent CD57+CD28-CD8+ T cells than patients with G0-1 RP at baseline, during dCRT, and at 1 month post-dCRT. These senescent cells exhibited increased granzyme B, IFN-γ, and TNF-α production. Higher baseline frequency of CD57+CD28-CD8+ T cells was an independent predictor of G2+ RP (hazard ratio, 8.42; 95% confidence interval, 2.58-27.45; P<0.001). Recursive partitioning analysis revealed three distinct risk groups stratified by baseline CD57+CD28-CD8+ T cell frequency and lung V20 Gy, with 1-year cumulative G2+ RP incidences of 50.0%, 16.7%, and 0% for high-, intermediate-, and low-risk groups, respectively (P=0.002).Higher baseline frequencies of CD57+CD28-CD8+ T cells correlated with increased G2+ RP risks. Our results suggest the need for further investigation of the role of T cell senescence on radiation-induced organ damage.
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