Evaluation of targeted and immune combination therapies in a rat model of hormone receptor-positive breast cancer [scRNA]

Breast cancer hormone receptor (HR) estrogen and progesterone (ER/PR) positive tumors were generated in an outbred rat model (Sprague-Dawley) through the injection of the carcinogen N-nitrosomethylurea (NMU). These tumors were treated with immune checkpoint blockade (anti PD-L1) in combination with targeted therapies, including an TBK1/IKBKE inhibitor, a KMT5B/C inhibitor, a TGF-b inhibitor, and a selective estrogen receptor degrader (SERD). This dataset includes single-cell RNA sequencing (scRNA-seq) data from tumors subjected to various treatment setups. Whole-tumor digestion was performed to preserve a comprehensive representation of the tumor microenvironment. The study aims to identify mechanisms that sensitize HR postive tumor subtypes to immune checkpoint blockade therapy.通过向远交系Sprague-Dawley大鼠模型注射致癌物N-亚硝基甲基脲（N-nitrosomethylurea, NMU），成功诱导生成了乳腺癌激素受体（hormone receptor, HR）阳性且雌激素受体（ER）、孕激素受体（PR）双阳性的肿瘤。上述肿瘤接受了免疫检查点阻断（anti-PD-L1）联合靶向治疗的干预，联用的靶向疗法包括TBK1/IKBKE抑制剂、KMT5B/C抑制剂、转化生长因子-β（TGF-β）抑制剂以及选择性雌激素受体降解剂（selective estrogen receptor degrader, SERD）。本数据集涵盖了经不同治疗方案处理后的肿瘤的单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）数据，实验采用全肿瘤消化法处理样本以完整保留肿瘤微环境的全貌。本研究旨在明确能够使HR阳性肿瘤亚型对免疫检查点阻断治疗产生敏感性的分子机制。