Institute for Cancer Research in People's Liberation Army, Xinqiao Hospital, Army Medical University, Chongqing, China.
Institute for Pathology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Cancer Med. 2020 May;9(10):3437-3444. doi: 10.1002/cam4.2987. Epub 2020 Mar 24.
There were no ideal markers to predict the development of radiation pneumonitis (RP). We want to investigate the value of variations of lymphocytes and T lymphocyte subsets in predicting RP after radiotherapy (RT) of lung cancer based on previous clinical findings. A total of 182 lung cancer patients who received RT were retrospectively analyzed. Circulating lymphocytes and T lymphocyte subsets were measured before, during, and after RT. Patients were evaluated from the start of RT to 6 months post-RT. A mice model with acute radiation-induced lung injury was established and circulating lymphocytes were measured weekly until 8 weeks after irradiation. Univariate and multivariate analyses were adopted to identify risk factors of RP. Lymphocyte levels significantly decreased (P < .001) in patients before RP symptoms developed that also was able to be seen in the mice model and the values recovered during remission of symptoms. The decrease in lymphocyte count reflected the severity of RP. Meanwhile, CD4 T lymphocyte count was significantly lower during the occurrence of symptoms in patients with RP than in those without RP (P < .001), and it improved along with RP recovery. Levels of lymphocytes and CD4 T lymphocyte subsets proved as independent predictors of RP. Here we showed that lower peripheral blood levels of lymphocytes and CD4 T lymphocyte were associated with an increased risk of RP, which was validated by this mice model, and thus are associated with differences in radiation-induced lung toxicity among individuals and help identify those who are susceptible to developing RP after RT.
目前尚无理想的标志物能够预测放射性肺炎(RP)的发生。我们希望基于既往临床发现,探讨放疗(RT)治疗肺癌后淋巴细胞和 T 淋巴细胞亚群变化对 RP 的预测价值。回顾性分析了 182 例接受 RT 的肺癌患者。在 RT 前后测量循环淋巴细胞和 T 淋巴细胞亚群。从开始 RT 到 RT 后 6 个月对患者进行评估。建立急性放射性肺损伤小鼠模型,每周测量循环淋巴细胞,直到照射后 8 周。采用单因素和多因素分析确定 RP 的危险因素。在发生 RP 症状之前,患者的淋巴细胞水平显著降低(P<0.001),在小鼠模型中也能看到这种情况,且在症状缓解期间恢复。淋巴细胞计数的减少反映了 RP 的严重程度。同时,与无 RP 患者相比,RP 患者在发生症状时 CD4+T 淋巴细胞计数明显较低(P<0.001),并且随着 RP 的恢复而改善。淋巴细胞和 CD4+T 淋巴细胞亚群水平是 RP 的独立预测因子。本研究表明,外周血淋巴细胞和 CD4+T 淋巴细胞水平较低与 RP 风险增加相关,这在小鼠模型中得到了验证,因此与个体间放射性肺毒性的差异相关,并有助于识别那些在 RT 后易发生 RP 的患者。