De Rosa Caterina, Morgillo Floriana, Amato Luisa, Iommelli Francesca, De Rosa Viviana, Tirino Virginia, Papaccio Federica, Tuccillo Concetta, Di Guida Gaetano, D'Angiolella Domenico Michele, Di Liello Alessandra, Zappavigna Silvia, Caraglia Michele, Gambardella Antonio, Nardone Valerio, Ramkumar Kavya, Wang Qi, Wang Jing, De Vita Ferdinando, Ciardiello Davide, Martinelli Erika, Troiani Teresa, Napolitano Stefania, Martini Giulia, Servetto Alberto, Byers Lauren Averett, Ciardiello Fortunato, Della Corte Carminia Maria
Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80131 Naples, Italy.
Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy.
iScience. 2025 Feb 1;28(3):111943. doi: 10.1016/j.isci.2025.111943. eCollection 2025 Mar 21.
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies to enhance immune responsiveness. Recent research explores combining DNA-damaging therapies with immunotherapy to activate the STING pathway and improve the antitumor immune response. The addition of DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs inhibitors, after chemotherapy has shown promise in activating innate immune sensors and enhancing CD8 T cell and NK cell pathways in SCLC models. This approach could potentially reshape the tumor microenvironment and sustain an antitumor immune response, offering a maintenance strategy for SCLC treatment.
小细胞肺癌（SCLC）是一种侵袭性很强的肺癌，治疗选择有限。患者通常对初始化疗免疫疗法反应良好，但很快就会复发，因此需要新的策略来增强免疫反应。最近的研究探索将DNA损伤疗法与免疫疗法相结合，以激活STING通路并改善抗肿瘤免疫反应。在化疗后添加DNA损伤修复（DDR）抑制剂，如DNA-PKcs抑制剂，已显示出在激活先天性免疫传感器以及增强SCLC模型中的CD8 T细胞和NK细胞通路方面具有前景。这种方法可能会重塑肿瘤微环境并维持抗肿瘤免疫反应，为SCLC治疗提供一种维持策略。
