Conventional therapy including chemo- and radiotherapy is the current standard treatment for cervical cancer. However, the cancer may become resistant to such modalities, necessitating the exploration of new therapeutic strategies. BRD4, an epigenetic reader that binds to acetylated histones and regulates transcription, plays a critical role in the development and progression of various cancers through its involvement in transcriptional regulation.

In this study, we examined the efficacy of BRD4 inhibition using different inhibitors in cervical cancer cells.

The organoid cultures derived from SiHa and HeLa cells were treated with three different BRD4 inhibitors (JQ1, MZ1, and AZD5153) at the concentration of 1 µM. The organoids were subjected to RNA extraction and whole transcriptome sequencing, respectively.

The results reveal that targeting BRD4 in the organoid model altered the expression of genes involved in immune response against tumor cells including PDCD1LG2, TGFB1, and NECTIN2. These genes are associated with immune cells targeting of tumor cells. Specifically, the downregulation of PDCD1LG2 (PDL2) suggested enhanced immune checkpoint pathways, while TGFB1 is known for its immunosuppressive functions and its roles in the tumor microenvironment. NECTIN2 is involved in immune cell adhesion and activation.

Targeting BRD4 has been shown to improve the immune response to tumors, suggesting its potential as a strategy for enhancing antitumor immunity in cancer treatment. These findings highlight the potential of BRD4 inhibitors to increase the efficacy of radiotherapy through enhancing immune response to tumor cells, which can also be activated by radiation, making BRD4 a promising therapeutic target for treating cervical cancer in combination with radiotherapy.