揭示多巴胺激动剂治疗在人泌乳素瘤肿瘤以及邻近基质细胞和免疫细胞中的正向和脱靶作用的潜在机制。对来自 3 名卡麦角林 (CBG) 治疗和 2 名初治患者的 5 例手术切除的泌乳素瘤进行了分析通过单细胞 RNA 测序 (scRNA-seq) 来比较细胞组成和转录情况。六种主要细胞群，包括肿瘤 (88.2%)、免疫细胞 (5.6%)、基质细胞 (4.9%)、祖细胞 (0.6%)、观察到增殖细胞（0.4%）和红细胞（0.2%）。 CBG 治疗患者的肿瘤细胞表达较低水平的调节激素分泌的基因，如 SCG2、VGF、TIMP1、NNAT 和 CALD1，这与 CBG 对激素加工和分泌的抑制作用一致。有趣的是，我们还观察到 CBG 处理的组织中 CD8 T 细胞数量增加。这些细胞毒性 CD8 T 细胞表达杀伤颗粒成分，例如穿孔素和颗粒酶 GZMB、GNLY 和 KLRD1 以及炎症细胞因子 CCL5。以隔室特异性方式进一步分析这些 CD8 T 细胞的免疫细胞激活，并注意到 CBG 处理样品的 CD8 T 细胞中 CD25 (IL2R) 表达增加。此外，并证实了之前的报告，我们注意到 CBG 处理的样本中基质细胞数量较高。我们的 scRNAseq 研究揭示了 CBG 处理和未处理的 PRLomas 在肿瘤和微环境细胞成分中转录组特征的关键差异，并且是首次描述了 CBG 治疗后 CD8 T 细胞先前未知的激活，这可能在 CBG 的杀肿瘤作用中发挥作用。© 作者 2024。由牛津大学出版社代表欧洲内分泌学会出版。

Unravel potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumor and neighboring stromal and immune cells.Five surgically resected prolactinomas from 3 cabergoline (CBG)-treated and 2 treatment naive patients were analyzed by single cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.Six major cell populations that included tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%) were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components, such as perforin and the granzymes GZMB, GNLY and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in CBG-treated samples.Our scRNAseq studies revealed key differences in the transcriptomic features of CBG-treated and untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time describe previously unknown activation of CD8+ T cells following CBG-treatment which may play a role in the tumoricidal actions of CBG.© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.