Breast tumor microenvironment structures are associated with genomic features and clinical outcome.
Breast tumor microenvironment structures are associated with genomic features and clinical outcome.
复制标题
乳腺肿瘤微环境结构与基因组特征和临床结果相关。
DOI：
10.1038/s41588-022-01041-y
复制
发表时间：
2022-05
期刊：
影响因子：
30.8
通讯作者：
Ali HR
中科院分区：
文献类型：
--
作者：
Danenberg E;Bardwell H;Zanotelli VRT;Provenzano E;Chin SF;Rueda OM;Green A;Rakha E;Aparicio S;Ellis IO;Bodenmiller B;Caldas C;Ali HR
肿瘤微环境(TME)的功能是由特定细胞的精确空间组织来协调的，但对TME内形成的多细胞结构知之甚少。在这里，我们系统地绘制了693个与基因组和临床数据相关的乳腺肿瘤的TME结构图，使用成像、质量细胞术和多层空间分析。我们确定了10个复发的TME结构，这些结构因血管含量、间质静止与激活以及白细胞组成而异。这些TME结构在乳腺癌亚型中有不同的浓缩模式，其中一些与指示免疫逃逸的基因组图谱有关。调节性T细胞和功能失调的T细胞同时出现在大的“抑制扩张”结构中。这些结构的特点是高度的细胞多样性，增殖的细胞和丰富的BRCA1和CASP8突变，预测雌激素受体阳性疾病的不良结局。这里显示的多细胞结构将保守的空间组织与局部的TME功能联系起来，并可以改善患者的分层。693例乳腺肿瘤的成像质量分析确定了10个复发的肿瘤微环境空间结构。这些结构在不同的分子亚型中丰富，并与基因组图谱和结果相关。
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. Imaging mass cytometry profiling of 693 breast tumors identified 10 recurrent tumor microenvironment spatial structures. These structures were enriched in different molecular subtypes and can be associated with genomic profiles and outcomes.
登录
查看更多内容
影响因子：
64.5
作者：
Levine JH;Simonds EF;Bendall SC;Davis KL;Amir el-AD;Tadmor MD;Litvin O;Fienberg HG;Jager A;Zunder ER;Finck R;Gedman AL;Radtke I;Downing JR;Pe'er D;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.5
作者：
Goltsev Y;Samusik N;Kennedy-Darling J;Bhate S;Hale M;Vazquez G;Black S;Nolan GP
通讯作者：
Nolan GP
影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
22.7
作者：
Ali, H. Raza;Jackson, Hartland W.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
结构细胞是器官特异性免疫反应的关键调节剂。
影响因子：
64.8
作者：
Krausgruber T;Fortelny N;Fife-Gernedl V;Senekowitsch M;Schuster LC;Lercher A;Nemc A;Schmidl C;Rendeiro AF;Bergthaler A;Bock C
通讯作者：
Bock C