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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-02-01 DOI:10.1016/j.isci.2025.111943

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 , Carminia Maria Della Corte

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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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抑制 DNA-PK 可维持小细胞肺癌的抗肿瘤先天免疫反应

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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