共同骨髓祖细胞 (CMP) 的浸润与乳腺癌中侵袭性较低的肿瘤生物学、较低的脑转移风险、更好的免疫治疗反应以及较高的患者生存率相关。
Infiltration of Common Myeloid Progenitor (CMP) Cells is Associated With Less Aggressive Tumor Biology, Lower Risk of Brain Metastasis, Better Response to Immunotherapy and Higher Patient Survival in Breast Cancer.
发表日期:2024 Jul 01
作者:
Masanori Oshi, Rongrong Wu, Thaer Khoury, Shipra Gandhi, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe
来源:
ANNALS OF SURGERY
摘要:
目的探讨常见髓系祖细胞(CMP)在乳腺肿瘤微环境(TME)中的临床相关性。稀有细胞在TME中的作用研究较少。对真实世界数据进行计算机转录组分析使我们能够检测和量化稀有细胞,包括 CMP 细胞。使用 xCell 算法对来自 SCAN-B、METABRIC 和 5 个单细胞序列队列的总共 5,176 名乳腺癌 (BC) 患者进行了分析。高组被定义为每个队列中超过三分之二的 CMP 评分。CMP 细胞由 0.07-0.25% 的乳腺肿瘤细胞组成,雌激素受体阳性 (ER) 细胞比三阴性 (TN) 亚型细胞 (0.1分别为免疫细胞的-0.75%、0.18-0.33%)。 CMP 细胞与 TME 中的任何骨髓谱系或干细胞均不相关。在 SCAN-B 和 METABRIC 队列中,较小肿瘤的 CMP 浸润较高,Nottingham 分级较低,并且 ER /HER2- 比 TNBC 一致。高 CMP 与较低的脑转移风险和更好的生存率显着相关,特别是在 ER /HER2- 中。高 CMP 丰富了上皮间质转化和血管生成途径,并减少了细胞增殖和 DNA 修复基因集。高 CMP ER /HER2- 与较少的免疫细胞浸润和细胞溶解活性相关 (P<0.001)。 ISPY-2 队列中 CMP 浸润与 ER /HER2- 和 TNBC 的新辅助化学免疫治疗反应相关(AUC 分别为 0.69 和 0.74)。 BC 中的 CMP 与细胞增殖和脑转移、对免疫治疗的更好反应和生存。这是首次报告 BC 省 CMP 浸润的临床相关性。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。
To investigate the clinical relevance of common myeloid progenitor (CMP) cells in breast tumor microenvironment (TME).The role of rare cells in TME is less studied. In Silico transcriptomic analyses of real-world data enable us to detect and quantify rare cells, including CMP cells.Total of 5,176 breast cancer (BC) patients from SCAN-B, METABRIC, and 5 single-cell sequence cohorts were analyzed using xCell algorithm. High group was defined as more than two thirds of CMP score in each cohort.CMP cells consist of 0.07-0.25% of bulk breast tumor cells, more in Estrogen Receptor-positive (ER+) compared with triple-negative (TN) subtype (0.1-0.75%, 0.18-0.33% of immune cells, respectively). CMP cells did not correlate with any of myeloid lineage nor stem cells in TME. CMP infiltration was higher in smaller tumors, with lower Nottingham grade, and in ER+/HER2- than in TNBC consistently in both SCAN-B and METABRIC cohorts. High CMP was significantly associated with lower risk of brain metastasis and with better survival, particularly in ER+/HER2- . High CMP enriched epithelial-to-mesenchymal transition and angiogenesis pathways, and less cell proliferation and DNA repair gene sets. High CMP ER+/HER2- was associated with less immune cell infiltration, and cytolytic activity (P<0.001). CMP infiltration correlated with neoadjuvant chemoimmunotherapy response for both ER+/HER2- and TNBC in the ISPY-2 cohort (AUC=0.69 and 0.74, respectively).CMP in BC is inversely associated with cell-proliferation and brain metastasis, better response to immunotherapy and survival. This is the first to report the clinical relevance of CMP infiltration in BC.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.