Vγ9Vδ2 T cell-mediated recognition of human solid tumors. Potential for immunotherapy of hepatocellular and colorectal carcinomas
| Autor: | Pascale Daniel, Karim Boudjema, Françoise Bouet-Toussaint, Florian Cabillic, Eric Dupont-Bierre, Olivier Toutirais, Véronique Catros, Cécile Thomas de La Pintière, Bernard Meunier, Noëlle Genetet, Matthieu Le Gallo |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research Carcinoma Hepatocellular T cell medicine.medical_treatment Immunology Lymphocyte Activation CXCR3 Immunotherapy Adoptive Natural killer cell Immune system Antigen T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cytotoxic T cell Receptors Immunologic business.industry Liver Neoplasms Receptors Antigen T-Cell gamma-delta Immunotherapy Flow Cytometry NKG2D digestive system diseases Phenotype medicine.anatomical_structure Oncology NK Cell Lectin-Like Receptor Subfamily K Receptors Natural Killer Cell Colorectal Neoplasms business Immunologic Memory |
| Zdroj: | Cancer Immunology, Immunotherapy. 57:531-539 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-007-0391-3 |
| Popis: | Vgamma9Vdelta2 T lymphocytes are reported to participate in the anti-tumor immune surveillance in human. They are known to recognize phosphoantigens and molecules expressed on cells undergoing neoplasic transformation. In this study, we investigated phenotype and anti-tumor cytotoxicity of ex vivo expanded Vgamma9Vdelta2 T cells in view of adoptive immunotherapy.Experiments were performed with peripheral blood samples from eleven patients [six colorectal carcinoma (CRC), four hepatocellular carcinoma (HCC), one sarcoma] and sixteen healthy donors.Ex vivo expansion of Vgamma9Vdelta2 T cells could be achieved by a single dose of phosphoantigen, either bromohydrin pyrophosphate or zoledronate, and supported by exogenous IL-2. After 2 weeks, expanded Vgamma9Vdelta2 T lymphocytes acquired the effector memory phenotype CD45RA(-)CD45RO(high)CD27(-). They expressed NKG2D and CD161 and the proinflammatory CXCR3 and CCR5 chemokine receptors. Vgamma9Vdelta2 T cells displayed a strong lytic activity toward a broad panel of tumor cell lines or primary cultures. Interestingly, HCC and CRC primary cells could be lysed by autologous Vgamma9Vdelta2 T cells whereas autologous normal cells were not sensitive to the lysis. mAbs blocking assays demonstrated that TCR was the most important receptor involved in the lysis of tumor cells. However, NKG2D receptor could deliver a costimulatory signal enhancing the lysis of HCC and CRC tumors expressing MICA/B. Treatment of tumor cells by the mevalonate pathway inhibitor, zoledronate, enhanced the killing of both HCC and CRC. Expansion index of Vgamma9Vdelta2 T cells was in similar levels in healthy donors or in cancer patients and total expansion was suitable for adoptive immunotherapy.These results provide a rationale for the clinical evaluation of Vgamma9Vdelta2 T lymphocytes in HCC and CRC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink