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Colon carcinoma cells induce CXCL11-dependent migration of CXCR3-expressing cytotoxic T lymphocytes in organotypic culture

Authors :
John P. Hoffman
Klara Berencsi
Pyapalli Rani
Dorothee Herlyn
Jiri Kalabis
Rolf Swoboda
Laura Caputo
Emma E. Furth
Neal J. Meropol
Elin R. Sigurdson
Tianqian Zhang
Rajasekharan Somasundaram
Francesco M. Marincola
Lydia R. Giles
Source :
Cancer Immunology, Immunotherapy. 56:359-370
Publication Year :
2006
Publisher :
Springer Science and Business Media LLC, 2006.

Abstract

Adoptive immunotherapy of cancer patients with cytolytic T lymphocytes (CTL) has been hampered by the inability of the CTL to home into tumors in vivo. Chemokines can attract T lymphocytes to the tumor site, as demonstrated in animal models, but the role of chemokines in T-lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the role of chemokines and their receptors in the migration of a colon carcinoma (CC) patient's CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic CC culture. CTL migration was mediated by chemokine receptor CXCR3 expressed by the CTL and CXCL11 chemokine secreted by the tumor cells. Excess CXCL11 or antibodies to CXCL11 or CXCR3 inhibited migration of CTL to tumor cells. T cell and tumor cell analyses for CXCR3 and CXCL11 expression, respectively, in ten additional CC samples, may suggest their involvement in other CC patients. Our studies, together with previous studies indicating angiostatic activity of CXCL11, suggest that CXCL11 may be useful as an immunotherapeutic agent for cancer patients when transduced into tumor cells or fused to tumor antigen-specific Ab.

Details

ISSN :
14320851 and 03407004
Volume :
56
Database :
OpenAIRE
Journal :
Cancer Immunology, Immunotherapy
Accession number :
edsair.doi.dedup.....5cfba5d1a2805a8dae16b5da15e71341
Full Text :
https://doi.org/10.1007/s00262-006-0190-2