Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein-α

被引：909

作者：

Kraman, Matthew ^{[1
]}

Bambrough, Paul J. ^{[1
]}

Arnold, James N. ^{[1
]}

Roberts, Edward W. ^{[1
]}

Magiera, Lukasz ^{[1
]}

Jones, James O. ^{[1
]}

Gopinathan, Aarthi ^{[2
,3
]}

Tuveson, David A. ^{[2
]}

Fearon, Douglas T. ^{[1
]}

机构：

[1] Univ Cambridge, MRC Ctr, Dept Med, Wellcome Trust Immunol Unit, Cambridge CB2 2QH, England

[2] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[3] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

来源：

SCIENCE | 2010年 / 330卷 / 6005期

基金：

英国惠康基金;

关键词：

IFN-GAMMA; T-CELLS; TUMOR PROGRESSION; HUMAN-MELANOMA; BONE-MARROW; CANCER; INHIBITION; GROWTH; DIFFERENTIATION; IMMUNOGENICITY;

D O I：

10.1126/science.1195300

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 stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. A stromal cell type that was first identified in human cancers expresses fibroblast activation protein-alpha (FAP). We created a transgenic mouse in which FAP-expressing cells can be ablated. Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-gamma and tumor necrosis factor-alpha. Depleting FAP-expressing cells in a subcutaneous model of pancreatic ductal adenocarcinoma also permitted immunological control of growth. Therefore, FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.

引用

页码：827 / 830

页数：4

共 30 条

[1] Fibroblast activation protein α identifies mesenchymal stromal cells from human bone marrow [J].