Guo Zhoubo, Zhang Kunning, Wei Xiaoying, Li Yanqi, Ma Xiaoxue, Li Yang, Han Dong, Du Qingwu, Zhang Tian, Chen Xi, Wei Hui, Yan Cihui, Zhang Wencheng, Pang Qingsong, Wang Ping
Departments of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhu West Road, Hexi District, Tianjin, China.
Department of Immunology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhu West Road, Hexi District, Tianjin, China.
J Leukoc Biol. 2023 Jan 10;113(1):11-17. doi: 10.1093/jleuko/qiac018.
Our previous phase Ib trial (NCT03222440) showed that radiotherapy plus the anti-PD-1 antibody camrelizumab is a safe and feasible first-line therapy for locally advanced esophageal squamous cell carcinoma. In this study, we divided peripheral CD8 T-cell differentiation subsets into 4 subpopulations (naive T cells, central memory T cells, effector memory T cells, and CD45RA+ effector memory T cells). We then investigated the influence of radiotherapy plus camrelizumab therapy on the proportions of the 4 subsets and their PD-1, TIGIT, and CTLA-4 expression as well as their proliferative activity and compared the effects with those of concurrent chemoradiotherapy. Nineteen and 15 patients with esophageal squamous cell carcinoma who received radiotherapy plus camrelizumab therapy and concurrent chemoradiotherapy, respectively, were enrolled in this study. We isolated peripheral blood mononuclear cells from these patients before treatment and longitudinally after the delivery of 40 Gy radiotherapy. Flow cytometry was conducted to detect peripheral CD8 T-cell subsets and PD-1, TIGIT, CTLA-4, and Ki67 expression levels in patients with esophageal squamous cell carcinoma. We found that radiotherapy plus camrelizumab therapy did not change the proportions of the 4 subsets or the expression of CTLA-4, but this therapy decreased PD-1 expression by the 4 subsets and TIGIT expression by effector memory T cells, as well as significantly enhanced the proliferative activity of CD8 T cells, whereas concurrent chemoradiotherapy produced different effects. In addition, we further identified peripheral biomarkers that potentially predict the outcome of radiotherapy plus camrelizumab therapy.
我们之前的Ib期试验（NCT03222440）表明，放疗联合抗PD-1抗体卡瑞利珠单抗是局部晚期食管鳞状细胞癌安全可行的一线治疗方案。在本研究中，我们将外周CD8 T细胞分化亚群分为4个亚群（初始T细胞、中央记忆T细胞、效应记忆T细胞和CD45RA +效应记忆T细胞）。然后，我们研究了放疗联合卡瑞利珠单抗治疗对这4个亚群比例及其PD-1、TIGIT和CTLA-4表达以及增殖活性的影响，并将其与同步放化疗的效果进行比较。本研究纳入了分别接受放疗联合卡瑞利珠单抗治疗和同步放化疗的19例和15例食管鳞状细胞癌患者。我们在治疗前以及40 Gy放疗后纵向采集这些患者的外周血单个核细胞。采用流式细胞术检测食管鳞状细胞癌患者外周CD8 T细胞亚群以及PD-1、TIGIT、CTLA-4和Ki67的表达水平。我们发现，放疗联合卡瑞利珠单抗治疗并未改变4个亚群的比例或CTLA-4的表达，但该治疗降低了这4个亚群的PD-1表达以及效应记忆T细胞的TIGIT表达，并显著增强了CD8 T细胞的增殖活性，而同步放化疗则产生了不同的效果。此外，我们进一步确定了可能预测放疗联合卡瑞利珠单抗治疗疗效的外周生物标志物。
