Antitumor Activity of T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model

¹Université Bordeaux 2 and ²Centre National de la Recherche Scientifique UMR 5164, and ³Laboratoire d'Immunologie et d'Immunogénétique, CHU Bordeaux, Bordeaux, France

^* To whom correspondence should be addressed. E-mail: myriam.capone{at}u-bordeaux2.fr.

	Abstract

T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that V2-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 V2^neg clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of V2^negclones, in contrast to V2⁺ cells, prevented the development of HT29 tumors. V2^neg 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 V2^neg 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 V2^neg clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific V2^neg cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy. [Cancer Res 2009;69(9):3971–8]

Key Words: human colon carcinoma, human T cells, mouse xenograft model, cytomegalovirus, chemokines