贝勒医学院张翔团队取得一项新突破。他们揭示了无偏的生态位标记绘制了骨转移中免疫排除的生态位。2026年4月28日，国际知名学术期刊《细胞》发表了这一成果。
为了不偏不倚地确定转移性生态位的细胞和分子特征，该课题组研究人员开发了基于分选酶的微环境生态位标记（SAMENT），它可以选择性地标记癌细胞在转移过程中遇到的细胞。在多种癌症模型和靶器官中应用SAMENT发现了共享的生态位特征，包括巨噬细胞富集和T细胞耗损，以及生态位巨噬细胞中显着的器官特异性表型异质性。在骨骼中，转移性壁龛中富含表达雌激素受体α (ERα)的巨噬细胞，并具有活跃的ERα信号传导。巨噬细胞中Esr1的条件缺失通过使T细胞浸润显著损害骨定植。ERα? 在多种癌症类型的人骨转移中也发现了巨噬细胞。总之，这些发现定义了一个独特的ERα并建立巨噬细胞ERα信号作为转移定殖过程中T细胞排斥的关键驱动因素。
据了解，转移癌细胞的命运是由局部微环境生态位决定的。
附：英文原文
Title: Unbiased niche labeling maps immune-excluded niche in bone metastasis
Author: Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L. Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G. Edwards, Hilda L. Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L. Satcher, Xiang H.-F. Zhang
Issue&Volume: 2026-04-28
Abstract: Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. ERα macrophages were also identified in human bone metastases across multiple cancer types. Together, these findings define a distinct ERα macrophage niche and establish macrophage ERα signaling as a key driver of T cell exclusion during metastatic colonization.
DOI: 10.1016/j.cell.2026.04.009
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00398-3