Kim Kyung Hwan, Pyo Hongryull, Lee Hoyoung, Oh Dongryul, Noh Jae Myoung, Ahn Yong Chan, Kim Chang Gon, Yoon Hong In, Lee Jiyun, Park Sehhoon, Jung Hyun-Ae, Sun Jong-Mu, Lee Se-Hoon, Ahn Jin Seok, Park Keunchil, Ku Bo Mi, Shin Eui-Cheol, Ahn Myung-Ju
Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Int J Radiat Oncol Biol Phys. 2023 Feb 1;115(2):464-475. doi: 10.1016/j.ijrobp.2022.07.018. Epub 2022 Jul 24.
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 CD57CD28CD8 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 CD57CD28CD8 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 CD57CD28CD8 T cell frequency and lung V, 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 CD57CD28CD8 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.
免疫衰老与放射性肺炎（RP）之间的关联在很大程度上尚不清楚。我们旨在确定一种外周血T细胞衰老生物标志物，以预测非小细胞肺癌（NSCLC）患者的RP。
前瞻性登记接受根治性同步放化疗（dCRT）的局部晚期NSCLC患者（队列1，n = 23；队列2，n = 31）。在基线、dCRT期间和dCRT后1个月采集外周血。患者被分为≥2级（G2+）RP和0-1级（G0-1）RP。进行流式细胞术以评估T细胞亚群的表型和功能特性。通过竞争风险分析估计RP发生率。
队列1和队列2中分别有5例和6例患者在dCRT后出现G2+ RP。在基线、dCRT期间和dCRT后1个月，G2+ RP患者比G0-1 RP患者表现出更老化的T细胞库和更高频率的衰老CD57CD28CD8 T细胞。这些衰老细胞表现出颗粒酶B、IFN-γ和TNF-α产生增加。CD57CD28CD8 T细胞的较高基线频率是G2+ RP的独立预测因子（风险比，8.42；95%置信区间，2.58-27.45；P<0.001）。递归划分分析显示，根据基线CD57CD28CD8 T细胞频率和肺V分为三个不同的风险组，高、中、低风险组的1年累积G2+ RP发生率分别为50.0%、16.7%和0%（P = 0.002）。
CD57CD28CD8 T细胞的较高基线频率与G2+ RP风险增加相关。我们的结果表明需要进一步研究T细胞衰老在辐射诱导的器官损伤中的作用。
