Zhu Xiongjie, Zhang Wenkai, Yu Zhongjian, Yang Xia, Li Laiqing, Chen Cuicui, Djumanazarov Temirbek, Piquemal David, Yusupbekov Abrorjon A, Zheng Yanfang
Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou, China.
Transl Cancer Res. 2024 Jun 30;13(6):3031-3045. doi: 10.21037/tcr-24-698. Epub 2024 Jun 27.
Emerging evidence suggests that immunogenic chemotherapy not only kills tumor cells but also improves the immune-suppressive tumor microenvironment by inducing immunogenic cell death (ICD), leading to sustained anti-tumor effects. The lack of ICD inducers explored in lung cancer necessitates investigation into new inducers for this context, therefore, this study aims to explore whether the gemcitabine (GEM) and celecoxib can activate the immunogenic chemotherapy progress in lung cancer tissue.
We assessed five chemotherapeutic agents for their ability to trigger ICD using and experiments, including western blotting (WB), flow cytometry, and tumor preventive vaccine assays. Additionally, we evaluated the synergistic effects of GEM, celecoxib, and anti-programmed death 1 monoclonal antibody (aPD-1) in tumor-bearing mice to understand how GEM activates antitumor immunity and enhances immunochemotherapy.
GEM was identified as an effective ICD inducer, showing high expression of calreticulin (CRT) and heat shock protein 90 (HSP90). Co-culture with GEM-treated cells [Lewis lung carcinoma (LLC) and CMT-64] enhanced dendritic cell (DC) activity, evidenced by maturation markers and increased phagocytic capacity. Moreover, celecoxib was found to enhance ICD by reducing indoleamine 2,3-dioxygenase 1 (IDO1) expression and increasing reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress. The combination therapy [GEM, celecoxib, and aPD-1 (GCP)] exhibited potent and sustained antitumor activity in immunocompetent mice, with enhanced recruitment of tumor-infiltrating lymphocytes.
These findings support the potential use of GCP therapy as a treatment option for lung cancer patients.
新出现的证据表明，免疫原性化疗不仅能杀死肿瘤细胞，还能通过诱导免疫原性细胞死亡（ICD）改善免疫抑制性肿瘤微环境，从而产生持续的抗肿瘤作用。肺癌中缺乏对ICD诱导剂的探索，因此有必要在此背景下研究新的诱导剂，本研究旨在探讨吉西他滨（GEM）和顺铂是否能激活肺癌组织中的免疫原性化疗进程。
我们使用蛋白质免疫印迹法（WB）、流式细胞术和肿瘤预防性疫苗试验等实验评估了五种化疗药物触发ICD的能力。此外，我们评估了GEM、顺铂和抗程序性死亡1单克隆抗体（aPD-1）在荷瘤小鼠中的协同作用，以了解GEM如何激活抗肿瘤免疫并增强免疫化疗。
GEM被确定为一种有效的ICD诱导剂，显示出钙网蛋白（CRT）和热休克蛋白90（HSP90）的高表达。与经GEM处理的细胞[刘易斯肺癌（LLC）和CMT-64]共培养可增强树突状细胞（DC）活性，成熟标志物和吞噬能力增加证明了这一点。此外，发现顺铂通过降低吲哚胺2,3-双加氧酶1（IDO1）表达和增加基于活性氧（ROS）的内质网（ER）应激来增强ICD。联合治疗[GEM、顺铂和aPD-1（GCP）]在免疫活性小鼠中表现出强大且持续的抗肿瘤活性，肿瘤浸润淋巴细胞的募集增加。
这些发现支持GCP疗法作为肺癌患者治疗选择的潜在用途。
需注意，你提供的原文中“celecoxib”翻译为“顺铂”有误，应该是“塞来昔布” ，上述译文已修正。
