PO.TB10.01 · 肿瘤生物学
浸润前乳腺癌中基质和免疫微环境的重编程
Reprogramming of the stromal and immune microenvironment in preinvasive breast cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
导管原位癌（DCIS）是最常见的浸润前乳腺癌形式。然而，我们对DCIS肿瘤微环境（TME）的了解仍然有限。在此，我们使用来自DCIS、浸润性乳腺癌和正常乳腺组织的新鲜组织样本，研究了雌激素受体阳性DCIS的TME。总计对来自153例患者的795,585个细胞进行单细胞RNA测序分析，并对39个样本采用空间转录组学方法（Visium、Xenium）进行检测。我们的数据鉴定出重编程的血管细胞、成纤维细胞和基底细胞，它们环绕DCIS区域，形成支持浸润前癌细胞的癌-基质环（CSL）。DCIS区域高度免疫抑制，仅有脂质巨噬细胞（APOC1+）和干扰素T细胞浸润。浸润前癌细胞表现出细胞周期和干扰素信号的激活，同时降低了细胞生长调控、RNA加工、分泌和细胞黏附。总的来说，这些数据显示DCIS中TME发生广泛的重塑，并在浸润性进展过程中持续存在。
查看英文原文 English abstract
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer. However, our knowledge of the DCIS tumor microenvironment (TME) remains limited. Here, we investigated the TME of estrogen receptor positive DCIS using fresh tissues samples from DCIS, invasive breast cancers and normal breast tissues. In total, 795,585 cells were analyzed from 153 patients by single cell RNA sequencing and 39 samples were profiled with spatial transcriptomics methods (Visium, Xenium). Our data identified reprogrammed vascular cells, fibroblasts and basal cells that encircled the DCIS regions, forming cancer stromal loops (CSL) that support the preinvasive cancer cells. The DCIS regions were highly immunosuppressive, and only lipomacrophages (APOC1+) and interferon T-cells infiltrated. The preinvasive cancer cells showed activation of cell cycling and interferon signaling, while reducing cell growth regulation, RNA processing, secretion and cell adhesion. Collectively, these data show extensive remodeling of the TME in DCIS that persists during invasive progression.
利益披露 Disclosure
S. He, None..
S. Bai, None..
C. Bethell, None..
E. Sei, None..
M. Rao, None..
T. Kumar, None..
C. Tang, None..
I. Marin, None..
J. Montalvan, None..
C. Nagi, None..
B. Lim, None.