浸润性导管性和小叶性乳腺癌的免疫景观显示出不同的巨噬细胞驱动的微环境。
Immune landscape in invasive ductal and lobular breast cancer reveals a divergent macrophage-driven microenvironment.
发表日期:2023 Mar 16
作者:
Sayali Onkar, Jian Cui, Jian Zou, Carly Cardello, Anthony R Cillo, Mostofa Rafid Uddin, April Sagan, Marion Joy, Hatice U Osmanbeyoglu, Katherine L Pogue-Geile, Priscilla F McAuliffe, Peter C Lucas, George C Tseng, Adrian V Lee, Tullia C Bruno, Steffi Oesterreich, Dario A A Vignali
来源:
Nature Cancer
摘要:
T细胞中心的免疫疗法到目前为止已经显示出对雌性激素受体阳性(ER +)乳腺癌有一定的临床益处。尽管占所有乳腺癌的70%,但相对于浸润性导管癌(IDC)和浸润性小叶癌(ILC)的妇女的ER +乳腺癌的免疫生物学知识仍然很少。为了研究这一点,我们对一组未经治疗的IDC(n = 94)和ILC(n = 87)肿瘤进行了表型、转录和功能分析。我们展示了巨噬细胞而不是T细胞是渗入肿瘤床和IDC和ILC之间最具转录多样性的细胞亚群。单元格邻域的分析揭示了在IDC但不是ILC中与较长无疾病生存期相关的巨噬细胞和T细胞之间的相互作用。我们的数据集为进一步探索ER + IDC和ILC中的免疫细胞动态提供了丰富的资源,并突出了巨噬细胞作为ER +乳腺癌的潜在靶点。©2023年。作者,通过Springer Nature America,Inc.独家许可。
T cell-centric immunotherapies have shown modest clinical benefit thus far for estrogen receptor-positive (ER+) breast cancer. Despite accounting for 70% of all breast cancers, relatively little is known about the immunobiology of ER+ breast cancer in women with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). To investigate this, we performed phenotypic, transcriptional and functional analyses for a cohort of treatment-naive IDC (n = 94) and ILC (n = 87) tumors. We show that macrophages, and not T cells, are the predominant immune cells infiltrating the tumor bed and the most transcriptionally diverse cell subset between IDC and ILC. Analysis of cellular neighborhoods revealed an interplay between macrophages and T cells associated with longer disease-free survival in IDC but not ILC. Our datasets provide a rich resource for further interrogation into immune cell dynamics in ER+ IDC and ILC and highlight macrophages as a potential target for ER+ breast cancer.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.