Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer

被引：492

作者：

Carstens, Julienne L. ^{[1
]}

de Sampaio, Pedro Correa ^{[1
]}

Yang, Dalu ^{[2
,3
]}

Barua, Souptik ^{[2
,3
]}

Wang, Huamin ^{[4
]}

Rao, Arvind ^{[2
,3
,5
]}

Allison, James P. ^{[6
]}

LeBleu, Valerie S. ^{[1
]}

Kalluri, Raghu ^{[1
,7
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Metastasis Res Ctr, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[3] Rice Univ, Dept Elect & Comp Engn, Houston, TX 77005 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[7] Rice Univ, Dept Bioengn, Houston, TX 77005 USA

[8] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

TUMOR MICROENVIRONMENT; IMMUNOTHERAPY; BLOCKADE; INFILTRATION; FIBROBLASTS; IMMUNITY; PD-1;

D O I：

10.1038/ncomms15095

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic Tcells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and alpha SMA(+) fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies.

引用

页数：13

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