Zhu Qian, Qiao Guoliang, Huang Lefu, Xu Chang, Guo Deliang, Wang Shuo, Zhao Jing, Song Yuguang, Liu Bing, Chen Zheng, Yang Zhiyong, Yuan Yufeng
Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Surgical Oncology, Massachusetts General Hospital, Boston, MA, United States.
Front Oncol. 2022 Apr 11;12:837560. doi: 10.3389/fonc.2022.837560. eCollection 2022.
We aimed to investigate the restoration of CD8PD-1 T cells through adoptive T-cell therapy (ACT) in relation to the prognosis and the therapeutic response to anti-PD-1 in patients with advanced pancreatic cancer (APC).
A total of 177 adult patients who underwent tumor resection as initial treatment for pancreatic ductal adenocarcinoma (PDAC) from February 2013 to July 2019 at Zhongnan Hospital of Wuhan University were enrolled in this study. Another cohort of 32 patients with APC was prospectively enrolled from Capital Medical University Cancer Center between June 1, 2013, and May 30, 2019.
Of the 177 patients who received tumor resection, 67 tumor samples showed overexpression of PD-L1 and 110 patients with low expression of PD-L1. We found that overexpressed PD-L1 was a significant prognostic factor related to overall survival (OS). Furthermore, we tested the percentage of peripheral CD8PD-1 T cells in all patients and found that it was significantly correlated with the PD-L1 expression and the prognosis of patients with PDAC. The peripheral blood T lymphocyte subtypes were tracked for 30 months, and CD8PD-1 cells were shown to decrease. After that, we performed ACT for patients with APC in another cancer center. We found that the ratios of posttreatment of ACT/pre-ACT CD8PD-1 T cells were significantly related to the prognosis of patients with APC. Moreover, patients with combined treatment of ACT with anti-PD-1 had significantly favorable OS.
This study showed that the CD8PD-1 T-cell level was related to the expression of PD-L1. Restoring CD8PD-1 T cells in patients with APC by treatment of ACT significantly benefits the prognosis and facilitates the response to anti-PD-1.
我们旨在研究通过过继性T细胞疗法（ACT）恢复CD8PD-1 T细胞与晚期胰腺癌（APC）患者的预后以及抗PD-1治疗反应之间的关系。
2013年2月至2019年7月在武汉大学中南医院接受肿瘤切除术作为胰腺导管腺癌（PDAC）初始治疗的177例成年患者纳入本研究。2013年6月1日至2019年5月30日期间，另一组32例APC患者前瞻性地从首都医科大学癌症中心纳入。
在177例接受肿瘤切除术的患者中，67例肿瘤样本显示PD-L1过表达，110例患者PD-L1低表达。我们发现，PD-L1过表达是与总生存期（OS）相关的显著预后因素。此外，我们检测了所有患者外周血CD8PD-1 T细胞的百分比，发现其与PD-L1表达及PDAC患者的预后显著相关。对患者外周血T淋巴细胞亚型进行了30个月的跟踪，结果显示CD8PD-1细胞减少。之后，我们在另一个癌症中心对APC患者进行了ACT治疗。我们发现，ACT治疗后/ACT治疗前CD8PD-1 T细胞的比率与APC患者的预后显著相关。此外，ACT联合抗PD-1治疗的患者总生存期显著更好。
本研究表明，CD8PD-1 T细胞水平与PD-L1表达有关。通过ACT治疗恢复APC患者的CD8PD-1 T细胞对预后有显著益处，并有助于对抗PD-1的反应。
