Human melanoma-specific CD8 + T-cells from metastases are capable of antigen-specific degranulation and cytolysis directly ex vivo - Sorbonne Université
Article Dans Une Revue OncoImmunology Année : 2014

Human melanoma-specific CD8 + T-cells from metastases are capable of antigen-specific degranulation and cytolysis directly ex vivo

Résumé

The relatively low frequencies of tumor Ag-specific T-cells in PBMC and metastases from cancer patients have long precluded the analysis of their direct ex vivo cytolytic capacity. Using a new composite technique that works well with low cell numbers, we aimed at determining the functional competence of melanoma-specific CD8(+) T-cells. A multiparameter flow cytometry based technique was applied to assess the cytolytic function, degranulation and IFNγ production by tumor Ag-specific CD8(+) T-cells from PBMC and tumor-infiltrated lymph nodes (TILN) of melanoma patients. We found strong cytotoxicity by T-cells not only when they were isolated from PBMC but also from TILN. Cytotoxicity was observed against peptide-pulsed target cells and melanoma cells presenting the naturally processed endogenous antigen. However, unlike their PBMC-derived counterparts, T-cells from TILN produced only minimal amounts of IFNγ, while exhibiting similar levels of degranulation, revealing a critical functional dichotomy in metastatic lesions. Our finding of partial functional impairment fits well with the current knowledge that T-cells from cancer metastases are so-called exhausted, a state of T-cell hyporesponsiveness also found in chronic viral infections. The identification of responsible mechanisms in the tumor microenvironment is important for improving cancer therapies.
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Dates et versions

hal-02569158 , version 1 (11-05-2020)

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Yolanda D Mahnke, Estelle Devevre, Petra Baumgaertner, Maurice Matter, Nathalie Rufer, et al.. Human melanoma-specific CD8 + T-cells from metastases are capable of antigen-specific degranulation and cytolysis directly ex vivo. OncoImmunology, 2014, 1 (4), pp.467-530. ⟨10.4161/onci.19856⟩. ⟨hal-02569158⟩
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