Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells

被引:118
作者
Brown, Christine E.
Vishwanath, Reena P.
Aguilar, Brenda
Starr, Renate
Najbauer, Joseph
Aboody, Karen S.
Jensen, Michael C.
机构
[1] City Hope Natl Med Ctr, Div Canc Immunotherapeut & Tumor Immunol, Duarte, CA 91010 USA
[2] City Hope Natl Med Ctr, Div Hematol & Hematopoiet Cell Transplantat, Med Ctr, Duarte, CA 91010 USA
[3] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA
关键词
D O I
10.4049/jimmunol.179.5.3332
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To exert a therapeutic effect, adoptively transferred tumor-specific CTLs must traffic to sites of tumor burden, exit the circulation, and infiltrate the tumor microenvironment. In this study, we examine the ability of adoptively transferred human CTL to traffic to tumors with disparate chemokine secretion profiles independent of tumor Ag recognition. Using a combination of in vivo tumor tropism studies and in vitro biophotonic chemotaxis assays, we observed that cell lines derived from glioma, medulloblastoma, and renal cell carcinoma efficiently chemoattracted ex vivo-expanded primary human T cells. We compared the chemokines secreted by tumor cell lines with high chernotactic activity with those that failed to elicit T cell chemotaxis (Daudi lymphoma, 10HTB neuroblastoma, and A2058 melanoma cells) and found a correlation between tumorderived production of MCP-1/CCL2 ( >= 10 ng/ml) and T cell chemotaxis. Chemokine immunodepletion studies confirmed that tumor-derived MCP-I elicits effector T cell chemotaxis. Moreover, MCP-I is sufficient for in vivo T cell tumor tropism as evidenced by the selective accumulation of Lv. administered firefly luciferase-expressing T cells in intracerebral xenografts of tumor transfectants secreting MCP-1. These studies suggest that the capacity of adoptively transferred T cells to home to tumors may be, in part, dictated by the species and amounts of tumor-derived chemokines, in particular MCP-1.
引用
收藏
页码:3332 / 3341
页数:10
相关论文
共 62 条
[1]  
Amann B, 1998, BRIT J UROL, V82, P118
[2]   Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2 [J].
Aragay, AM ;
Mellado, M ;
Frade, JMR ;
Martin, AM ;
Jimenez-Sainz, MC ;
Martinez-A, C ;
Mayor, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) :2985-2990
[3]   Cancer and the chemokine network [J].
Balkwill, F .
NATURE REVIEWS CANCER, 2004, 4 (07) :540-550
[4]   Optical imaging of Renilla luciferase reporter gene expression in living mice [J].
Bhaumik, S ;
Gambhir, SS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (01) :377-382
[5]   Cancer immunotherapy: A treatment for the masses [J].
Blattman, JN ;
Greenberg, PD .
SCIENCE, 2004, 305 (5681) :200-205
[6]   Biophotonic cytotoxicity assay for high-throughput screening of cytolytic killing [J].
Brown, CE ;
Wright, CL ;
Naranjo, A ;
Vishwanath, RP ;
Chang, WC ;
Olivares, S ;
Wagner, JR ;
Bruins, L ;
Raubitschek, A ;
Cooper, LJN ;
Jensen, MC .
JOURNAL OF IMMUNOLOGICAL METHODS, 2005, 297 (1-2) :39-52
[7]   Lymphotactin expression by engineered myeloma cells drives tumor regression:: Mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor [J].
Cairns, CM ;
Gordon, JR ;
Li, F ;
Baca-Estrada, ME ;
Moyana, T ;
Xiang, J .
JOURNAL OF IMMUNOLOGY, 2001, 167 (01) :57-65
[8]   MONOCYTE CHEMOATTRACTANT PROTEIN-1 ACTS AS A T-LYMPHOCYTE CHEMOATTRACTANT [J].
CARR, MW ;
ROTH, SJ ;
LUTHER, E ;
ROSE, SS ;
SPRINGER, TA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (09) :3652-3656
[9]   Photonic detection of bacterial pathogens in living hosts [J].
Contag, CH ;
Contag, PR ;
Mullins, JI ;
Spilman, SD ;
Stevenson, DK ;
Benaron, DA .
MOLECULAR MICROBIOLOGY, 1995, 18 (04) :593-603
[10]   Luciferase Imaging of neurotropic viral infection in intact animals [J].
Cook, SH ;
Griffin, DE .
JOURNAL OF VIROLOGY, 2003, 77 (09) :5333-5338