Kang Pengyuan, Yu Hong, Li Yunfei, Wen Xue, Ye Hua, Luo Yuhao, Yang Yaqi, Yuan Qing, Lin Sheng
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province 646000, China.
Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province 646000, China.
J Oncol. 2023 Jan 31;2023:3221510. doi: 10.1155/2023/3221510. eCollection 2023.
Hypofractionated radiotherapy (HFRT) or chemotherapy combined with programmed death-1 (PD-1) blockade has achieved good clinical control in advanced nonsmall cell lung cancer (NSCLC). However, the relative influence of HFRT + PD-1 blockade and chemo-immunotherapy on peripheral memory T cell subsets in NSCLC responders has not been evaluated in clinical practice. Thirty-nine patients with advanced NSCLC were enrolled. The frequencies of naive (Tn; CD45RACCR7), central memory (Tcm; CD45RACCR7), effector memory (Tem; CD45RACCR7), and effector memory RA (TemRA; CD45RACCR7) T cell subsets and PD-1 expression were analyzed in CD4 and CD8 T cells using flow cytometry from peripheral blood samples. The correlations of memory T cell subsets and PD-1 expression with overall survival in HFRT + PD-1 blockade group were examined using the Kaplan-Meier method. Patients with partial response to HFRT + PD-1 blockade showed reduction in Tn and expansion in TemRA cell subpopulations among CD8 T cells and reduced PD-1CD4 and PD-1CD8 T cells, all of which were significantly correlated with overall survival. The responders to chemo-immunotherapy showed expansion of the TemRA and decrease of Tcm in CD8 T cell subpopulation. Our findings show that HFRT+PD-1 blockade and chemo-immunotherapy combination therapies induce differential memory T cell subset differentiation, offering predictive markers for treatment response. Clinical Trial Information: https://clinicaltrials.gov/ct2/show/ChiCTR-1900027768.
大分割放疗（HFRT）或化疗联合程序性死亡-1（PD-1）阻断在晚期非小细胞肺癌（NSCLC）中已取得良好的临床控制效果。然而，在临床实践中，HFRT + PD-1阻断和化疗免疫疗法对NSCLC缓解者外周记忆T细胞亚群的相对影响尚未得到评估。招募了39例晚期NSCLC患者。使用流式细胞术对外周血样本中的CD4和CD8 T细胞进行分析，以检测初始（Tn；CD45RA⁺CCR7⁺）、中央记忆（Tcm；CD45RA⁻CCR7⁺）、效应记忆（Tem；CD45RA⁻CCR7⁻）和效应记忆RA（TemRA；CD45RA⁺CCR7⁻）T细胞亚群的频率以及PD-1表达。使用Kaplan-Meier方法检查HFRT + PD-1阻断组中记忆T细胞亚群和PD-1表达与总生存期的相关性。对HFRT + PD-1阻断有部分反应的患者，其CD8 T细胞中的Tn减少，TemRA细胞亚群扩增，PD-1⁺CD4和PD-1⁺CD8 T细胞减少，所有这些均与总生存期显著相关。化疗免疫疗法的缓解者在CD8 T细胞亚群中表现为TemRA扩增和Tcm减少。我们的研究结果表明，HFRT + PD-1阻断和化疗免疫疗法联合治疗可诱导不同的记忆T细胞亚群分化，为治疗反应提供预测标志物。临床试验信息：https://clinicaltrials.gov/ct2/show/ChiCTR-1900027768 。
