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Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis

Cancer cells exploit CD47 overexpression to inhibit phagocytic elimination and neoantigen processing via the myeloid CD47-SIRPα axis and thereby indirectly evade adaptive T cell immunity. Here, we report on a hitherto unrecognized direct immunoinhibitory feature of cancer cell-expressed CD47. We unc...

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Autores principales: Hendriks, Mark A.J.M., Britsch, Isabel, Ke, Xiurong, van Wijngarden, Anne P., Samplonius, Douwe F., Ploeg, Emily M., Helfrich, Wijnand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632294/
https://www.ncbi.nlm.nih.gov/pubmed/34858730
http://dx.doi.org/10.1080/2162402X.2021.2005344
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author Hendriks, Mark A.J.M.
Britsch, Isabel
Ke, Xiurong
van Wijngarden, Anne P.
Samplonius, Douwe F.
Ploeg, Emily M.
Helfrich, Wijnand
author_facet Hendriks, Mark A.J.M.
Britsch, Isabel
Ke, Xiurong
van Wijngarden, Anne P.
Samplonius, Douwe F.
Ploeg, Emily M.
Helfrich, Wijnand
author_sort Hendriks, Mark A.J.M.
collection PubMed
description Cancer cells exploit CD47 overexpression to inhibit phagocytic elimination and neoantigen processing via the myeloid CD47-SIRPα axis and thereby indirectly evade adaptive T cell immunity. Here, we report on a hitherto unrecognized direct immunoinhibitory feature of cancer cell-expressed CD47. We uncovered that in response to IFNγ released during cognate T cell immune attack, cancer cells dynamically enhance CD47 cell surface expression, which coincides with acquiring adaptive immune resistance toward pro-apoptotic effector T cell mechanisms. Indeed, CRISPR/Cas9-mediated CD47-knockout rendered cancer cells more sensitive to cognate T cell immune attack. Subsequently, we developed a cancer-directed strategy to selectively overcome CD47-mediated adaptive immune resistance using bispecific antibody (bsAb) CD47xEGFR-IgG2s that was engineered to induce rapid and prolonged cancer cell surface displacement of CD47 by internalization. Treatment of CD47(pos) cancer cells with bsAb CD47xEGFR-IgG2s potently enhanced susceptibility to cognate CD8(pos) T cells. Targeting CD47-mediated adaptive immune resistance may open up new avenues in cancer immunotherapy.
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spelling pubmed-86322942021-12-01 Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis Hendriks, Mark A.J.M. Britsch, Isabel Ke, Xiurong van Wijngarden, Anne P. Samplonius, Douwe F. Ploeg, Emily M. Helfrich, Wijnand Oncoimmunology Research Article Cancer cells exploit CD47 overexpression to inhibit phagocytic elimination and neoantigen processing via the myeloid CD47-SIRPα axis and thereby indirectly evade adaptive T cell immunity. Here, we report on a hitherto unrecognized direct immunoinhibitory feature of cancer cell-expressed CD47. We uncovered that in response to IFNγ released during cognate T cell immune attack, cancer cells dynamically enhance CD47 cell surface expression, which coincides with acquiring adaptive immune resistance toward pro-apoptotic effector T cell mechanisms. Indeed, CRISPR/Cas9-mediated CD47-knockout rendered cancer cells more sensitive to cognate T cell immune attack. Subsequently, we developed a cancer-directed strategy to selectively overcome CD47-mediated adaptive immune resistance using bispecific antibody (bsAb) CD47xEGFR-IgG2s that was engineered to induce rapid and prolonged cancer cell surface displacement of CD47 by internalization. Treatment of CD47(pos) cancer cells with bsAb CD47xEGFR-IgG2s potently enhanced susceptibility to cognate CD8(pos) T cells. Targeting CD47-mediated adaptive immune resistance may open up new avenues in cancer immunotherapy. Taylor & Francis 2021-11-20 /pmc/articles/PMC8632294/ /pubmed/34858730 http://dx.doi.org/10.1080/2162402X.2021.2005344 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hendriks, Mark A.J.M.
Britsch, Isabel
Ke, Xiurong
van Wijngarden, Anne P.
Samplonius, Douwe F.
Ploeg, Emily M.
Helfrich, Wijnand
Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title_full Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title_fullStr Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title_full_unstemmed Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title_short Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
title_sort cancer cells under immune attack acquire cd47-mediated adaptive immune resistance independent of the myeloid cd47-sirpα axis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632294/
https://www.ncbi.nlm.nih.gov/pubmed/34858730
http://dx.doi.org/10.1080/2162402X.2021.2005344
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