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

gamma delta T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that V delta 2-negative ((neg)) gamma delta 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 delta 2(neg) clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of V delta 2(neg)clones, in contrast to V delta 2(+) cells, prevented the development of HT29 tumors. V delta 2(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 delta and monocyte chemoattractant protein-4. More importantly, a systemic i.p. treatment with V delta 2(neg) clones delayed the growth of HT29 s.c. tumors. The effect of in vivo gamma delta T-cell passive immunotherapy on tumor growth could be reverted by addition of a blocking anti-CCR3 antibody. gamma delta T-cell passive immunotherapy was dependent on the cytotoxic activity of the gamma delta effectors toward their targets because V delta 2(neg) clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific V delta 2(neg) cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy. [Cancer Res 2009;69(9):3971-8]