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

Published: 14 February 2023| Version 1 | DOI: 10.17632/xxmsvk9fck.1
, Shuailong Zhang,


Based on clinical samples from the TCGA database, we analyzed the expression of PRKDC in various types of cancers using Timer online analysis software and compared them with the normal group. In addition we also used Timer to analyze the immune cell infiltration in breast invasive carcinomas with different amplified copy numbers of PRKDC, which provided clinical data to support the results of our subsequent experiments.In cellular experiments, we treated the human-derived triple-negative breast cancer cell line BT549 with the DNA-PKcs inhibitor NU7441 and performed transcriptome sequencing analysis of the drug-treated BT549 cells compared to the untreated group.In addition, we also examined the changes of cytoplasmic nucleic acid sensing pathways in three cell lines, BT549, MDA-MB-231, and CH12F3, after drug addition using MTT, ELISA, Western blot, RNA Extraction and Quantitative PCR and other experimental methods.In animal experiments, we treated normal BALB/c female mice with NU7441 and examined the effect of the drug on immunity by ELISA, flow cytometry and other experimental methods.In addition, we also used mouse breast cancer cell line 4T1 to construct Xenograft mouse model in Female immune competent BALB/c mice and athymic nude BALB/c mice.NU7441 treatment was followed by ELISA, Immunohistochemistry, flow cytometry and other assays to detect the effects of drug treatment on tumor immune cell infiltration and anti-tumor immunity.



Dalian Medical University


Interferon, Tumor Micromilieu, Triple-Negative Breast Cancer