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

Abstract

Abstract;D T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that VD2-negative ( neg ) ;D 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 VD2 neg clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of VD2 neg clones, in contrast to VD2 + cells, prevented the development of HT29 tumors. VD2 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-1D and monocyte chemoattractant protein-4. More importantly, a systemic i.p. treatment with VD2 neg clones delayed the growth of HT29 s.c. tumors. The effect of in vivo ;D T-cell passive immunotherapy on tumor growth could be reverted by addition of a blocking anti-CCR3 antibody. ;D T-cell passive immunotherapy was dependent on the cytotoxic activity of the ;D effectors toward their targets because VD2 neg clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific VD2 neg cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy. [Cancer Res 2009;69(9):3971-8]

Cytomegalovirus-Induced γδ T Cells Associate with Reduced Cancer Risk after Kidney Transplantation

“…25 Moreover, we recently reported on the ability of human CMV-specific V␦2 neg ␥␦ T cells to inhibit tumor cell development in vivo in a model of human tumor xenograft in immunodeficient mice. 26 Taken together, our previous findings have suggested that the ␥␦ T cells that were amplified during CMV infection may also be involved in tumor surveillance. In this report, we have examined the relationship between CMV-induced ␥␦ T cells and in vivo cancer occurrence in KTRs.…”

Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukaemia

“…In this context, the recent demonstration in a murine xenograft model that gd T cells, reactive against cytomegalovirus infected cells, exhibit anti-tumour activity is of interest. 22 The major cause of treatment failure in patients allografted for refractory AML is disease relapse. In this study, pre-transplant tumour burden is identified as an important determinant of relapse.…”

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

“…17 Orthotopic xenografts of the HT29 colon cancer cells in mice infused with human TCRVd2 2 cd T lymphocytes also carried cd TILs that impaired tumor development. 18 In prostate and breast tumors, however, Vd1 1 cd TILs are rather immunosuppressive for dendritic cells and T cells 19 and favor the growth of the tumor through IL-10 release. 20 The second hallmark of T lymphocytes expected to attack tumors is their histocompatibility leukocyte antigen-unrestricted cytotoxic capacity for cancer cells, as well as their ability to secrete adequate cytokines.…”