Targeting DNA-PKcs promotes anti-tumoral immunity via triggering cytosolic DNA sensing and inducing an inflamed tumor immuno-microenvironment in metastatic triple-negative breast cancer
作者机构：College of Basic Medical SciencesDalian Medical UniversityDalianLiaoning 116044China Liaoning Provincial Key Laboratory of Medical Molecular BiologyDalianLiaoning 116044China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2023年第10卷第5期
页 面：1809-1811页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：immunity inflammation interferon
摘 要：Triple-negative breast cancer(TNBC)is highly malignant and refractory to immunotherapy through impeding the immune cell infiltration and inflammation in the tumor microenvironment(TME).1 DNA-dependent protein kinase catalytic subunit(DNA-PKcs)is a member of the phosphatidylinositol 3-kinase-related kinase family,which is required for the non-homologous end joining repair.2 The effect of DNA-PKcs on the generation of cytosolic DNA and inflammation response in tumor immuno-environment is not *** found a specific DNA-PKcs inhibitor,NU7441,induced cytosolic DNA,stimulator of interferon genes(STING),and retinoic acid-inducible gene I(RIG-I)signals in *** Balb/c immune-competent mice bearing 4T1 TNBC cells,NU7441 impaired the tumor growth and metastasis,and increased the CD45+leukocytes,CD4+T cells,CD8+T cells,and CD1a+antigen-presenting cells,as well as MHC-I and interferon alpha receptor(IFNAR)in ***,in Balb/c athymic nude mice without IFNAR and CD8+T cells in TME,NU7741 did not influence tumor *** results show that inhibition of DNA-PKcs triggers cytosolic DNA sensing and induces an inflamed TME to promote anti-tumoral immunity,which provides a strategy to alter the inflammation and lymphocyte infiltration in TME to increase the efficacy of immunotherapy in TNBC and other cancers with an immune-suppressive TME.
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