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High Proliferative Capacity and Specific Antiautologous Melanoma Cytotoxicity of a Human T-Lymphocyte Clone Derived from Tumor-Infiltrating Lymphocytes

Abstract : A CD8+ clone, identified by its T-cell receptor gamma- and beta-gene configuration, was shown to preferentially develop, in the bulk culture of melanoma tumor-infiltrating lymphocytes with recombinant interleukin 2 after 1 month. Thirteen CD8+ clones were obtained by limiting dilution culture of tumor-infiltrating lymphocytes from 43-days old culture. Four of these clones, analyzed for T-cell receptor rearrangements, exhibited exactly the same T-cell receptor gene pattern as tumor-infiltrating lymphocytes from the bulk culture, showing, therefore, that all the CD8+ clones were subclones. All the 13 CD8+ subclones were strongly cytotoxic for autologous melanoma cells but did not kill K562. A more complete cytotoxicity analysis showed that the clones did not kill autologous fibroblasts or Con A blasts or allogeneic tumor targets. Furthermore, specific killing was inhibited by monoclonal antibodies against CD3, CD8, T-cell receptors alpha beta, and class I major histocompatibility complex antigens indicating that effector-to-target cell recognition was mediated through the T-cell receptor in a major histocompatibility complex-restricted fashion. These data showed that human melanoma-specific cytotoxic T lymphocytes can be obtained from melanoma TIL and that a single cytotoxic T lymphocyte clone can be expanded to more than 10(10) cells without a loss of autotumor specificity.
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https://www.hal.inserm.fr/inserm-03351869
Contributor : Nadine Gervois Connect in order to contact the contributor
Submitted on : Wednesday, September 22, 2021 - 4:13:42 PM
Last modification on : Thursday, September 23, 2021 - 8:03:29 AM

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Nadine Gervois, Fran~oise Heuze, Elisabeth Diez, Francine Jotereau. High Proliferative Capacity and Specific Antiautologous Melanoma Cytotoxicity of a Human T-Lymphocyte Clone Derived from Tumor-Infiltrating Lymphocytes. Human Immunology, Elsevier, 1990, 28 (2), pp.112-8. ⟨10.1016/0198-8859(90)90006-b⟩. ⟨inserm-03351869⟩

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