Chromobox 2 (CBX2) 是一种表观遗传解读器，也是 Polycomb 阻遏物复合物 1 (PRC1) 的组成部分，在 > 75% 的高级别浆液性癌 (HGSC) 中高度表达。 CBX2 表达增加与较差的生存率相关，而 CBX2 敲低则导致化疗敏感性提高。在 HGSC 免疫活性小鼠模型中，CBX2 的敲低可减缓肿瘤进展。我们试图探索 CBX2 的调节对肿瘤免疫微环境 (TIME) 的影响，了解 TIME 在疾病进展和治疗耐药性发展中发挥着关键作用。对现有数据集的探索表明，CBX2 表达升高与 TIME 中的特定免疫细胞类型显着相关。 RNA-seq 和差异表达基因的通路分析证明了免疫特征富集。共聚焦显微镜和共培养实验发现，CBX2 的调节会导致巨噬细胞的招募和浸润增加。与 CBX2 过表达细胞培养的巨噬细胞的流式细胞术显示 M2 样巨噬细胞增加，吞噬活性降低。 Trp53、Brca2 缺失 ID8 同基因小鼠模型 (ID8 Trp53-/- Brca2-/-) 中的 Cbx2 敲低导致与对照相比肿瘤进展减少。 NanoString 免疫肿瘤学小组分析表明，Cbx2 的敲低会改变免疫细胞组成，巨噬细胞增加。多光谱免疫组织化学进一步证实巨噬细胞浸润增加。 CBX2 表达增加会导致促肿瘤巨噬细胞的募集和极化，靶向 CBX2 可能有助于调节 TIME，从而增强免疫疗法的功效。

Chromobox 2 (CBX2), an epigenetic reader and component of Polycomb Repressor Complex 1 (PRC1), is highly expressed in >75% of high-grade serous carcinoma (HGSC). Increased CBX2 expression is associated with poorer survival, while CBX2 knockdown leads to improved chemotherapy sensitivity. In an HGSC immune competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with the specific immune cell types in the TIME. RNA-seq and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2 overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53, Brca2 null ID8 syngeneic murine model (ID8 Trp53-/- Brca2-/-) led to decreased tumor progression compared to control. NanoString Immuno-Oncology Panel analysis suggested knock down in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of pro-tumor macrophages and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies.