| Literature DB >> 29123081 |
Jingjing Zhu1,2,3, Céline G Powis de Tenbossche1,2, Stefania Cané1,2,3, Didier Colau1,2, Nicolas van Baren1,2, Christophe Lurquin1,2, Anne-Marie Schmitt-Verhulst4, Peter Liljeström5, Catherine Uyttenhove1,2, Benoit J Van den Eynde6,7,8.
Abstract
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates the tumoral resistance signature observed in human melanomas. TiRP tumors resist immunotherapy based on checkpoint blockade, cancer vaccines or adoptive T-cell therapy. TiRP tumors recruit and activate tumor-specific CD8+ T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, which are rejected after adoptive T-cell therapy. Apoptosis of tumor-infiltrating lymphocytes can be prevented by interrupting the Fas/Fas-ligand axis, and is triggered by polymorphonuclear-myeloid-derived suppressor cells, which express high levels of Fas-ligand and are enriched in TiRP tumors. Blocking Fas-ligand increases the anti-tumor efficacy of adoptive T-cell therapy in TiRP tumors, and increases the efficacy of checkpoint blockade in transplanted tumors. Therefore, tumor-infiltrating lymphocytes apoptosis is a relevant mechanism of immunotherapy resistance, which could be blocked by interfering with the Fas/Fas-ligand pathway.Entities:
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Year: 2017 PMID： 29123081 PMCID： PMC5680273 DOI： 10.1038/s41467-017-00784-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919