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

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.