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.
DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer / 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. - In: ISCIENCE. - ISSN 2589-0042. - 28:3(2025). [10.1016/j.isci.2025.111943]
DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer
Servetto, Alberto;
2025
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
