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Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis

CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocyti...

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Autores principales: He, Yuan, Bouwstra, Renee, Wiersma, Valerie R., de Jong, Mathilde, Jan Lourens, Harm, Fehrmann, Rudolf, de Bruyn, Marco, Ammatuna, Emanuele, Huls, Gerwin, van Meerten, Tom, Bremer, Edwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358615/
https://www.ncbi.nlm.nih.gov/pubmed/30710089
http://dx.doi.org/10.1038/s41467-018-08013-z
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author He, Yuan
Bouwstra, Renee
Wiersma, Valerie R.
de Jong, Mathilde
Jan Lourens, Harm
Fehrmann, Rudolf
de Bruyn, Marco
Ammatuna, Emanuele
Huls, Gerwin
van Meerten, Tom
Bremer, Edwin
author_facet He, Yuan
Bouwstra, Renee
Wiersma, Valerie R.
de Jong, Mathilde
Jan Lourens, Harm
Fehrmann, Rudolf
de Bruyn, Marco
Ammatuna, Emanuele
Huls, Gerwin
van Meerten, Tom
Bremer, Edwin
author_sort He, Yuan
collection PubMed
description CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does not impact on phagocytosis induction by CD20 antibody rituximab nor associates with overall survival of Diffuse Large B-Cell Lymphoma patients. In contrast, expression of CD47 negatively impacts on overall and progression free survival. In conclusion, cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy.
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spelling pubmed-63586152019-02-04 Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis He, Yuan Bouwstra, Renee Wiersma, Valerie R. de Jong, Mathilde Jan Lourens, Harm Fehrmann, Rudolf de Bruyn, Marco Ammatuna, Emanuele Huls, Gerwin van Meerten, Tom Bremer, Edwin Nat Commun Article CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does not impact on phagocytosis induction by CD20 antibody rituximab nor associates with overall survival of Diffuse Large B-Cell Lymphoma patients. In contrast, expression of CD47 negatively impacts on overall and progression free survival. In conclusion, cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy. Nature Publishing Group UK 2019-02-01 /pmc/articles/PMC6358615/ /pubmed/30710089 http://dx.doi.org/10.1038/s41467-018-08013-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
He, Yuan
Bouwstra, Renee
Wiersma, Valerie R.
de Jong, Mathilde
Jan Lourens, Harm
Fehrmann, Rudolf
de Bruyn, Marco
Ammatuna, Emanuele
Huls, Gerwin
van Meerten, Tom
Bremer, Edwin
Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title_full Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title_fullStr Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title_full_unstemmed Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title_short Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
title_sort cancer cell-expressed slamf7 is not required for cd47-mediated phagocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358615/
https://www.ncbi.nlm.nih.gov/pubmed/30710089
http://dx.doi.org/10.1038/s41467-018-08013-z
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