CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.

Détails

ID Serval
serval:BIB_23B0FDB46E86
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.
Périodique
Oncoimmunology
Auteur(s)
Leignadier J., Favre S., Luther S.A., Luescher I.F.
ISSN
2162-4011 (Print)
ISSN-L
2162-4011
Statut éditorial
Publié
Date de publication
2016
Volume
5
Numéro
3
Pages
e1086861
Langue
anglais
Résumé
Cytotoxic T lymphocytes (CTL) from CD8β-deficient mice have powerful FasL-mediated cytotoxicity and IFNγ responses, but ablated Ca(2+) and NFAT signaling, which can be restored by transduction with CD8β. Upon infection with lymphocytic choriomeningitis virus (LCMV), these cells yielded GP33-specific CTL (CD8βR) that exhibited high FasL/Fas-mediated cytotoxicity, IFNγ CXCL9 and 10 chemokine responses. Transfer of these cells in B16-GP33 tumor bearing mice resulted in (i) massive T cell tumor infiltration, (ii) strong reduction of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg) and IL-17-expressing T helper cells, (iii) maturation of tumor-associated antigen-presenting cells and (iv) production of endogenous, B16 melanoma-specific CTL that eradicated the tumor long after the transferred CD8βR CTL perished. Our study demonstrates that the synergistic combination of strong Fas/FasL mediated cytotoxicity, IFNγ and CXCL9 and 10 responses endows adoptively transferred CTL to reprogram the tumor environment and to thus enable the generation of endogenous, tumoricidal immunity.
Pubmed
Web of science
Création de la notice
13/05/2016 8:07
Dernière modification de la notice
20/08/2019 14:01
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