Durable antitumor responses to CD47 blockade require adaptive immune stimulation
Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47-SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy.
Errataetall: |
CommentIn: Immunol Lett. 2016 Dec;180:73-74. - PMID 27662791 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2016 |
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Erschienen: |
2016 |
Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
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Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 113(2016), 19 vom: 10. Mai, Seite E2646-54 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Sockolosky, Jonathan T [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 13.12.2016 Date Revised 30.03.2022 published: Print-Electronic CommentIn: Immunol Lett. 2016 Dec;180:73-74. - PMID 27662791 Citation Status MEDLINE |
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doi: |
10.1073/pnas.1604268113 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM259530247 |
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500 | |a Citation Status MEDLINE | ||
520 | |a Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47-SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a T cell | |
650 | 4 | |a cancer | |
650 | 4 | |a immunotherapy | |
650 | 4 | |a macrophage | |
650 | 4 | |a protein engineering | |
650 | 7 | |a Antibodies, Monoclonal, Murine-Derived |2 NLM | |
650 | 7 | |a Antineoplastic Agents |2 NLM | |
650 | 7 | |a CD47 Antigen |2 NLM | |
650 | 7 | |a Cancer Vaccines |2 NLM | |
700 | 1 | |a Dougan, Michael |e verfasserin |4 aut | |
700 | 1 | |a Ingram, Jessica R |e verfasserin |4 aut | |
700 | 1 | |a Ho, Chia Chi M |e verfasserin |4 aut | |
700 | 1 | |a Kauke, Monique J |e verfasserin |4 aut | |
700 | 1 | |a Almo, Steven C |e verfasserin |4 aut | |
700 | 1 | |a Ploegh, Hidde L |e verfasserin |4 aut | |
700 | 1 | |a Garcia, K Christopher |e verfasserin |4 aut | |
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