DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer

DNA-PK抑制可维持小细胞肺癌中的抗肿瘤先天免疫反应

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作者:Caterina De Rosa ,Floriana Morgillo ,Luisa Amato ,Francesca Iommelli ,Viviana De Rosa ,Virginia Tirino ,Federica Papaccio ,Concetta Tuccillo ,Gaetano Di Guida ,Domenico Michele D'Angiolella ,Alessandra Di Liello ,Silvia Zappavigna ,Michele Caraglia ,Antonio Gambardella ,Valerio Nardone ,Kavya Ramkumar ,Qi Wang ,Jing Wang ,Ferdinando De Vita ,Davide Ciardiello ,Erika Martinelli ,Teresa Troiani ,Stefania Napolitano ,Giulia Martini ,Alberto Servetto ,Lauren Averett Byers ,Fortunato Ciardiello ,Carminia Maria Della Corte

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.

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