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

Détails

Ressource 1Télécharger: BIB_C1CE647640D2.P001.pdf (1297.06 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_C1CE647640D2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Human melanoma-specific CD8(+) T-cells from metastases are capable of antigen-specific degranulation and cytolysis directly ex vivo.
Périodique
Oncoimmunology
Auteur(s)
Mahnke Y.D., Devevre E., Baumgaertner P., Matter M., Rufer N., Romero P., Speiser D.E.
ISSN
2162-402X (Electronic)
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
1
Numéro
4
Pages
467-530
Langue
anglais
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.
Pubmed
Création de la notice
22/11/2012 15:25
Dernière modification de la notice
03/03/2018 21:08
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