PD-1治疗非小细胞肺癌（NSCLC）患者的疗效仍不令人满意。激活 STING 通路是提高 PD-1 抑制剂疗效的一种有前景的策略。在这里，我们发现粉防己碱（TET）是一种从中药常用药用植物中提取的抗肿瘤化合物，具有抑制非小细胞肺癌肿瘤生长的能力。从机制上讲，TET 诱导核 DNA 损伤并增加胞质 dsDNA，从而激活 STING/TBK1/IRF3 通路，进而促进小鼠体内树突状细胞 (DC)、巨噬细胞以及 CD8 T 细胞的肿瘤浸润。体内成像动态监测TET治疗后STING通路活性的增加，并预测肿瘤免疫微环境的激活。我们进一步发现，TET与αPD-1单克隆抗体（αPD-1 mAb）联合使用，可通过促进CD8 T细胞浸润并增强其细胞杀伤作用，产生显着的抗癌作用，从而减少肿瘤的生长，延长肿瘤的生存时间。 NSCLC 小鼠的存活率。因此，TET通过激活STING通路有效消除NSCLC细胞并增强免疫治疗疗效，TET与抗PD-1免疫治疗的结合值得进一步探索应用。版权所有©2024作者。由爱思唯尔有限公司出版。保留所有权利。

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.