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

γδ T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that Vδ2-negative (neg) γδ T lymphocytes isolated from transplant recipients infected by cytomegalovirus (CMV) killed both CMV-infected cells and HT29 colon cancer c...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-05, Vol.69 (9), p.3971-3978
Main Authors: DEVAUD, Christel, BILHERE, Eric, LOIZON, Séverine, PITARD, Vincent, BEHR, Charlotte, MOREAU, Jean-François, DECHANET-MERVILLE, Julie, CAPONE, Myriam
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Infectious diseases
Life Sciences
Medical sciences
Pharmacology. Drug treatments
Tumors
Viral diseases
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Summary:γδ T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that Vδ2-negative (neg) γδ 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 Vδ2neg clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of Vδ2negclones, in contrast to Vδ2+ cells, prevented the development of HT29 tumors. Vδ2neg 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-1δ and monocyte chemoattractant protein-4. More importantly, a systemic i.p. treatment with Vδ2neg clones delayed the growth of HT29 s.c. tumors. The effect of in vivo γδ T-cell passive immunotherapy on tumor growth could be reverted by addition of a blocking anti-CCR3 antibody. γδ T-cell passive immunotherapy was dependent on the cytotoxic activity of the γδ effectors toward their targets because Vδ2neg clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific Vδ2neg cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy. [Cancer Res 2009;69(9):3971–8]
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-08-3037