Cargando…
CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells
The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593563/ https://www.ncbi.nlm.nih.gov/pubmed/34816102 http://dx.doi.org/10.1016/j.isci.2021.103348 |
_version_ | 1784599770242744320 |
---|---|
author | Qadir, Abdul S. Guégan, Jean Philippe Ginestier, Christophe Chaibi, Assia Bessede, Alban Charafe-Jauffret, Emmanuelle Macario, Manon Lavoué, Vincent Rouge, Thibault de la Motte Law, Calvin Vilker, Jacob Wang, Hongbin Stroup, Emily Schipma, Matthew J. Bridgeman, Bryan Murmann, Andrea E. Ji, Zhe Legembre, Patrick Peter, Marcus E. |
author_facet | Qadir, Abdul S. Guégan, Jean Philippe Ginestier, Christophe Chaibi, Assia Bessede, Alban Charafe-Jauffret, Emmanuelle Macario, Manon Lavoué, Vincent Rouge, Thibault de la Motte Law, Calvin Vilker, Jacob Wang, Hongbin Stroup, Emily Schipma, Matthew J. Bridgeman, Bryan Murmann, Andrea E. Ji, Zhe Legembre, Patrick Peter, Marcus E. |
author_sort | Qadir, Abdul S. |
collection | PubMed |
description | The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer (TNBC) cells prevents tumor growth by modulating the immune landscape. CD95-deficient, but not wild-type, tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by infiltrating NK cells and does not involve T cells or macrophages. In contrast, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities on NK cells, providing a new target for immune therapy. |
format | Online Article Text |
id | pubmed-8593563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85935632021-11-22 CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells Qadir, Abdul S. Guégan, Jean Philippe Ginestier, Christophe Chaibi, Assia Bessede, Alban Charafe-Jauffret, Emmanuelle Macario, Manon Lavoué, Vincent Rouge, Thibault de la Motte Law, Calvin Vilker, Jacob Wang, Hongbin Stroup, Emily Schipma, Matthew J. Bridgeman, Bryan Murmann, Andrea E. Ji, Zhe Legembre, Patrick Peter, Marcus E. iScience Article The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer (TNBC) cells prevents tumor growth by modulating the immune landscape. CD95-deficient, but not wild-type, tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by infiltrating NK cells and does not involve T cells or macrophages. In contrast, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities on NK cells, providing a new target for immune therapy. Elsevier 2021-10-29 /pmc/articles/PMC8593563/ /pubmed/34816102 http://dx.doi.org/10.1016/j.isci.2021.103348 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Qadir, Abdul S. Guégan, Jean Philippe Ginestier, Christophe Chaibi, Assia Bessede, Alban Charafe-Jauffret, Emmanuelle Macario, Manon Lavoué, Vincent Rouge, Thibault de la Motte Law, Calvin Vilker, Jacob Wang, Hongbin Stroup, Emily Schipma, Matthew J. Bridgeman, Bryan Murmann, Andrea E. Ji, Zhe Legembre, Patrick Peter, Marcus E. CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title | CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title_full | CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title_fullStr | CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title_full_unstemmed | CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title_short | CD95/Fas protects triple negative breast cancer from anti-tumor activity of NK cells |
title_sort | cd95/fas protects triple negative breast cancer from anti-tumor activity of nk cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593563/ https://www.ncbi.nlm.nih.gov/pubmed/34816102 http://dx.doi.org/10.1016/j.isci.2021.103348 |
work_keys_str_mv | AT qadirabduls cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT gueganjeanphilippe cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT ginestierchristophe cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT chaibiassia cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT bessedealban cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT charafejauffretemmanuelle cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT macariomanon cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT lavouevincent cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT rougethibaultdelamotte cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT lawcalvin cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT vilkerjacob cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT wanghongbin cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT stroupemily cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT schipmamatthewj cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT bridgemanbryan cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT murmannandreae cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT jizhe cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT legembrepatrick cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells AT petermarcuse cd95fasprotectstriplenegativebreastcancerfromantitumoractivityofnkcells |