CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.
- Leignadier J Ludwig Center for Cancer Research, University of Lausanne , Epalinges, Switzerland.
- Favre S Department of Biochemistry, University of Lausanne , Epalinges, Switzerland.
- Luther SA Department of Biochemistry, University of Lausanne , Epalinges, Switzerland.
- Luescher IF Ludwig Center for Cancer Research, University of Lausanne , Epalinges, Switzerland.
- 2016-05-04
Published in:
- Oncoimmunology. - 2016
English
Cytotoxic T lymphocytes (CTL) from CD8β-deficient mice have powerful FasL-mediated cytotoxicity and IFNγ responses, but ablated Ca2+ 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.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1080/2162402X.2015.1086861
- PMID 27141342
- Persistent URL
- https://sonar.ch/global/documents/277949
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