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Immunology |

T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model1 Université Bordeaux 2 and 2 Centre National de la Recherche Scientifique UMR 5164, and 3 Laboratoire d'Immunologie et d'Immunogénétique, CHU Bordeaux, Bordeaux, France
Requests for reprints: Myriam Capone, UMR-Centre National de la Recherche Scientifique 5164, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France. Phone: 33-05-57-57-14-71; Fax: 33-05-57-57-14-72; E-mail: myriam.capone{at}u-bordeaux2.fr.
Key Words: human colon carcinoma human
T cells mouse xenograft model cytomegalovirus chemokines

T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that V
2-negative (neg) 
T lymphocytes isolated from transplant recipients infected by cytomegalovirus (CMV) killed both CMV-infected cells and HT29 colon cancer cells in vitro. To investigate the antitumor effects of V
2neg clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of V
2negclones, in contrast to V
2+ cells, prevented the development of HT29 tumors. V
2neg clones expressed chemokine C-C motif receptor 3 (CCR3) and migrated in vitro in response to chemokines secreted by HT29 cells, among which were the CCR3 ligands macrophage inflammatory protein-1
and monocyte chemoattractant protein-4. More importantly, a systemic i.p. treatment with V
2neg clones delayed the growth of HT29 s.c. tumors. The effect of in vivo 
T-cell passive immunotherapy on tumor growth could be reverted by addition of a blocking anti-CCR3 antibody. 
T-cell passive immunotherapy was dependent on the cytotoxic activity of the 
effectors toward their targets because V
2neg clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific V
2neg cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy. [Cancer Res 2009;69(9):3971–8]
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L. Couzi, Y. Levaillant, A. Jamai, V. Pitard, R. Lassalle, K. Martin, I. Garrigue, O. Hawchar, F. Siberchicot, N. Moore, et al. Cytomegalovirus-Induced {gamma}{delta} T Cells Associate with Reduced Cancer Risk after Kidney Transplantation J. Am. Soc. Nephrol., January 1, 2010; 21(1): 181 - 188. [Abstract] [Full Text] [PDF] |
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