小柯机器人

乳腺肿瘤微环境结构与基因组特征和临床结果有关
2022-04-20 14:53

近日,英国剑桥大学H. Raza Ali等研究人员合作发现,乳腺肿瘤微环境结构与基因组特征和临床结果有关。相关论文于2022年4月18日在线发表在《自然—遗传学》杂志上。

研究人员利用成像质谱仪和与基因组和临床数据相关的693个乳腺肿瘤的多层空间分析,系统地绘制了肿瘤微环境(TME)的原位结构。研究人员确定了10个反复出现的TME结构,这些结构因血管内容、基质静止与激活以及白细胞组成而不同。这些TME结构在乳腺癌亚型中具有独特的富集模式,有些与表明免疫逃逸的基因组图谱有关。调节性和功能失调的T细胞共同出现在大型的"抑制性扩张"结构中。

这些结构的特点是高细胞多样性、增殖细胞和富集BRCA1和CASP8突变,并预测了雌激素受体阳性疾病的结果不佳。这些多细胞结构将保守的空间组织与局部的TME功能联系起来,有望改善病人的分层。

据了解,TME的功能是由特化细胞的精确空间组织协调的,然而对TME内形成的多细胞结构却知之甚少。

附:英文原文

Title: Breast tumor microenvironment structures are associated with genomic features and clinical outcome

Author: Danenberg, Esther, Bardwell, Helen, Zanotelli, Vito R. T., Provenzano, Elena, Chin, Suet-Feung, Rueda, Oscar M., Green, Andrew, Rakha, Emad, Aparicio, Samuel, Ellis, Ian O., Bodenmiller, Bernd, Caldas, Carlos, Ali, H. Raza

Issue&Volume: 2022-04-18

Abstract: The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in situ using imaging mass cytometry and multitiered spatial analysis of 693 breast tumors linked to genomic and clinical data. We identified ten recurrent TME structures that varied by vascular content, stromal quiescence versus activation, and leukocyte composition. These TME structures had distinct enrichment patterns among breast cancer subtypes, and some were associated with genomic profiles indicative of immune escape. Regulatory and dysfunctional T cells co-occurred in large ‘suppressed expansion’ structures. These structures were characterized by high cellular diversity, proliferating cells and enrichment for BRCA1 and CASP8 mutations and predicted poor outcome in estrogen-receptor-positive disease. The multicellular structures revealed here link conserved spatial organization to local TME function and could improve patient stratification.

DOI: 10.1038/s41588-022-01041-y

Source: https://www.nature.com/articles/s41588-022-01041-y

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

分享到:

0