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Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma

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Abstract

We have taken advantage of a recently described technique of transformation and immortalization of T lymphocytes using the lymphotropic Herpesvirus saimiri, to achieve long-lasting T-cell lines from gastric cancer patients and healthy volunteers. Blood samples were drawn and T lymphocytes were transformed. Once sustained growth was observed, lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. Cytofluorometric analysis revealed that CD3 and CD45 were found at lower proportion in primary cells from patients than from control individuals (54% vs 75%, p<0.001, 90% vs 96%, p<0.05, respectively), and in HVS-derived T-cell lines (90% vs 98%, p<0.05, 97% vs 100%, p<0.05, respectively). Proliferative analyses showed that primary isolated cells were unable to respond adequately to CD3-, CD2-, and PHA-mediated stimulation, as compared to controls. Similarly, T-cell lines from patients proliferated to a lesser extent when CD3- and CD2-mediated stimuli were considered, especially when simultaneous stimulation via CD3 and CD2 molecules was carried out (47,824 counts per minute [cpm] vs 121,478 cpm, p<0.05). Altogether these results show that the defects reported in T cells from patients with cancer are not exclusively due to tumour-derived factors, since the alterations persist in long-lasting, HVS-transformed, T-cell lines, suggesting that this model seems a suitable one to disclose them.

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Acknowledgements

This work was supported by a FIS grant (99/0999). We thank the Centro de Técnicas Inmunológicas (Universidad Complutense de Madrid) for technical support, Pilar Lucea, Paloma del Pico, and Genoveva Vallejo for help in the shipment of samples, and Ángeles Mencía for help in growing cell lines.

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Authors and Affiliations

  1. Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Pabellón 5, 4ª planta, 28040, Madrid, Spain

    A. P. Valeri, M. Pérez-Blas, M. López-Santalla, N. Aguilera, C. Rodríguez-Juan, L. Sala-Silveira & J. M. Martín-Villa

  2. Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain

    A. Gutiérrez, J. Martín, I. Lasa, J. M. Mugüerza, A. López, L. García-Sancho & J. Granell

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  1. A. P. Valeri
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  2. M. Pérez-Blas
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  3. A. Gutiérrez
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  4. M. López-Santalla
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  5. N. Aguilera
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  6. C. Rodríguez-Juan
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  7. L. Sala-Silveira
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  8. J. Martín
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  9. I. Lasa
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  10. J. M. Mugüerza
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  11. A. López
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  12. L. García-Sancho
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  13. J. Granell
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  14. J. M. Martín-Villa
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Correspondence to J. M. Martín-Villa.

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APV and MP-B should be considered as joint first authors

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Valeri, A.P., Pérez-Blas, M., Gutiérrez, A. et al. Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma. Cancer Immunol Immunother 52, 708–714 (2003). https://doi.org/10.1007/s00262-003-0413-8

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  • DOI: https://doi.org/10.1007/s00262-003-0413-8

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