新的证据表明，免疫原性化疗不仅可以杀死肿瘤细胞，还可以通过诱导免疫原性细胞死亡（ICD）来改善免疫抑制性肿瘤微环境，从而产生持续的抗肿瘤作用。由于缺乏针对肺癌的 ICD 诱导剂，因此需要研究新的诱导剂，因此，本研究旨在探讨吉西他滨 (GEM) 和塞来昔布是否可以激活肺癌组织中的免疫原性化疗进展。我们评估了五种化疗药物的他们能够使用离体和体内实验触发 ICD，包括蛋白质印迹 (WB)、流式细胞术和肿瘤预防疫苗测定。此外，我们还评估了GEM、塞来昔布和抗程序性死亡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被鉴定为有效的ICD诱导剂，显示钙网蛋白 (CRT) 和热休克蛋白 90 (HSP90) 的高表达。与 GEM 处理的细胞 [刘易斯肺癌 (LLC) 和 CMT-64] 共培养增强了树突状细胞 (DC) 活性，成熟标记物和吞噬能力增强证明了这一点。此外，塞来昔布被发现通过减少吲哚胺 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。联合疗法 [GEM、塞来昔布和 aPD-1 (GCP)] 在免疫功能正常的小鼠中表现出有效且持续的抗肿瘤活性，并增强了肿瘤浸润淋巴细胞的募集。这些发现支持 GCP 疗法作为肺癌治疗选择的潜在用途癌症患者。2024 年转化癌症研究。版权所有。

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 ex vivo and in vivo 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.2024 Translational Cancer Research. All rights reserved.