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:	Mark A.J.M. Hendriks, Isabel Britsch, Xiurong Ke, Anne P. van Wijngarden, Douwe F. Samplonius, Emily M. Ploeg, Wijnand Helfrich
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	cd47 resistance t cell-induced cytotoxicity bispecific antibody cancer immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/98669fa6874142af8bbb8031277bb690
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spelling	oai:doaj.org-article:98669fa6874142af8bbb8031277bb6902021-11-26T11:19:49ZCancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis2162-402X10.1080/2162402X.2021.2005344https://doaj.org/article/98669fa6874142af8bbb8031277bb6902021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.2005344https://doaj.org/toc/2162-402XCancer 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 CD47pos cancer cells with bsAb CD47xEGFR-IgG2s potently enhanced susceptibility to cognate CD8pos T cells. Targeting CD47-mediated adaptive immune resistance may open up new avenues in cancer immunotherapy.Mark A.J.M. HendriksIsabel BritschXiurong KeAnne P. van WijngardenDouwe F. SamploniusEmily M. PloegWijnand HelfrichTaylor & Francis Grouparticlecd47resistancet cell-induced cytotoxicitybispecific antibodycancer immunotherapyImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cd47 resistance t cell-induced cytotoxicity bispecific antibody cancer immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	cd47 resistance t cell-induced cytotoxicity bispecific antibody cancer immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mark A.J.M. Hendriks Isabel Britsch Xiurong Ke Anne P. van Wijngarden Douwe F. Samplonius Emily M. Ploeg Wijnand Helfrich Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis
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 CD47pos cancer cells with bsAb CD47xEGFR-IgG2s potently enhanced susceptibility to cognate CD8pos T cells. Targeting CD47-mediated adaptive immune resistance may open up new avenues in cancer immunotherapy.
format	article
author	Mark A.J.M. Hendriks Isabel Britsch Xiurong Ke Anne P. van Wijngarden Douwe F. Samplonius Emily M. Ploeg Wijnand Helfrich
author_facet	Mark A.J.M. Hendriks Isabel Britsch Xiurong Ke Anne P. van Wijngarden Douwe F. Samplonius Emily M. Ploeg Wijnand Helfrich
author_sort	Mark A.J.M. Hendriks
title	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_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_sort	cancer cells under immune attack acquire cd47-mediated adaptive immune resistance independent of the myeloid cd47-sirpα axis
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/98669fa6874142af8bbb8031277bb690
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Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis

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