Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes
Autor: | Anne-Marie Schmitt-Verhulst, Peter Liljeström, Céline Powis de Tenbossche, Didier Colau, Nicolas van Baren, Jingjing Zhu, Stefania Canè, Benoît Van den Eynde, Catherine Uyttenhove, Christophe Lurquin |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Fas Ligand Protein medicine.medical_treatment Science Melanoma Experimental General Physics and Astronomy Apoptosis Mice Transgenic Cancer Vaccines Immunotherapy Adoptive General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine Lymphocytes Tumor-Infiltrating Cancer immunotherapy Cell Line Tumor medicine Tumor Microenvironment Animals Humans fas Receptor lcsh:Science Tumor microenvironment immunotherapy Immunosuppression Multidisciplinary business.industry Tumor-infiltrating lymphocytes Melanoma Cancer General Chemistry Immunotherapy Fas receptor medicine.disease Immune checkpoint 030104 developmental biology Editorial 030220 oncology & carcinogenesis Immunology Female lcsh:Q business Immunosuppression |
Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) British Journal of Cancer |
ISSN: | 2041-1723 |
Popis: | 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. |
Databáze: | OpenAIRE |
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