Antitumor activity of gammadelta T cells reactive against cytomegalovirus-infected cells in a mouse xenograft tumor model.
gammadelta T cells recognize stress-induced autoantigens and contribute to immunity against infections and cancer. Our previous study revealed that Vdelta2-negative ((neg)) gammadelta 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 Vdelta2(neg) clones in vivo, we generated hypodermal HT29 tumors in immunodeficient mice. Concomitant injections of Vdelta2(neg)clones, in contrast to Vdelta2(+) cells, prevented the development of HT29 tumors. Vdelta2(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-1delta and monocyte chemoattractant protein-4. More importantly, a systemic i.p. treatment with Vdelta2(neg) clones delayed the growth of HT29 s.c. tumors. The effect of in vivo gammadelta T-cell passive immunotherapy on tumor growth could be reverted by addition of a blocking anti-CCR3 antibody. gammadelta T-cell passive immunotherapy was dependent on the cytotoxic activity of the gammadelta effectors toward their targets because Vdelta2(neg) clones were not able to inhibit the growth of A431 hypodermal tumors. Our findings suggest that CMV-specific Vdelta2(neg) cells could target in vivo cancer cells, making them an attractive candidate for antitumor immunotherapy.
Devaud
Christel
C
Laboratoire d'Immunologie et d'Immunogénétique, Université Bordeaux 2 and Centre National de la Recherche Scientifique UMR 5164, CHU Bordeaux, Bordeaux, France.
Bilhere
Eric
E
Loizon
Séverine
S
Pitard
Vincent
V
Behr
Charlotte
C
Moreau
Jean-François
JF
Dechanet-Merville
Julie
J
Capone
Myriam
M
D000818:Animals; D018938:Caco-2 Cells; D018925:Chemokines / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D054397:Receptors, CCR3 / Q000096:biosynthesis; D054367:Receptors, CXCR3 / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D018925:Chemokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054397:Receptors, CCR3; D054367:Receptors, CXCR3