阻断PD-L1的免疫治疗对三阴性乳腺癌（TNBC）效果不佳，亟需探索新策略提高疗效。小分子JQ1通过结合溴化结构域蛋白BRD4下调癌基因MYC表达，引起PD-L1及CD47的下调表达，从而提高自然杀伤T细胞和巨噬细胞对肿瘤的识别。光热治疗具有杀伤肿瘤并增强肿瘤抗原释放的作用。据此提出利用小分子JQ1联合光热治疗，通过增强肿瘤抗原递呈和免疫细胞对肿瘤的识别，提高TNBC疗效的假说。本项目拟利用仿生材料黑色素纳米颗粒为载体高效装载JQ1，建立生物发光皮下瘤及转移瘤动物模型，探索单次/多次联合治疗对免疫细胞、细胞因子及肿瘤疗效的影响；利用MR/光声/光学成像可视化示踪肿瘤的生长和转移；探索BRD4关键调控因子小RNA（miR-29b）对JQ1免疫调节作用的影响，预测miR-29b成为联合调控靶点的可能性，进一步研究其作用机制。预期该诊疗新策略为TNBC免疫调控、免疫治疗及机制研究提供新思路。

The immunotherapy through blocking the expression of PD-L1 is not effective for triple-negative breast cancer (TNBC). It is urgent to explore new strategies to improve the efficacy. Small molecule JQ1 can down-regulate the expression of oncogene MYC by binding to brominated domain protein BRD4, resulting in the down-regulation of PD-L1 and CD47, in order to improve the recognition of cytotoxic T lymphocytes and macrophages to tumors. Photothermal therapy can kill tumors and enhance the release of tumor antigens. Therefore, we propose that small molecule JQ1 combined with photothermal therapy could improve the therapeutic effect of TNBC by enhancing the presentation of tumor antigen and the recognition of immune cells. This project intends to use biomimetic polymers melanin nanoparticles as carriers to efficiently load JQ1. Bioluminescent subcutaneous and metastases tumor animal models will be established to observe the immune cells, cytokines and tumor efficacy after single/multiple photothermal immunotherapy. The MR/photoacoustic/optical imaging will track the occurrence and development of tumors. The effect of microRNA (miR-29b), a key regulator of BRD4, on JQ1 immune regulation will be further explored, and be predicted as a target for joint regulation. And the mechanism will be next studied. Such a novel photothermal immunotherapy strategy may provide a potential expectation for immuno-regulation, immunotherapy and mechanisms research for triple-negative breast cancer.