دورية أكاديمية
IgA-Mediated Killing of Tumor Cells by Neutrophils Is Enhanced by CD47-SIRPα Checkpoint Inhibition.
| العنوان: | IgA-Mediated Killing of Tumor Cells by Neutrophils Is Enhanced by CD47-SIRPα Checkpoint Inhibition. |
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| المؤلفون: | Treffers LW; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Ten Broeke T; Immunotherapy Laboratory, Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Rösner T; Section for Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, Christian-Albrechts-University, Kiel, Germany., Jansen JHM; Immunotherapy Laboratory, Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., van Houdt M; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Kahle S; Section for Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, Christian-Albrechts-University, Kiel, Germany., Schornagel K; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Verkuijlen PJJH; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Prins JM; Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, the Netherlands., Franke K; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Kuijpers TW; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., van den Berg TK; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands., Valerius T; Section for Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, Christian-Albrechts-University, Kiel, Germany., Leusen JHW; Immunotherapy Laboratory, Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Matlung HL; Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. h.matlung@sanquin.nl. |
| المصدر: | Cancer immunology research [Cancer Immunol Res] 2020 Jan; Vol. 8 (1), pp. 120-130. Date of Electronic Publication: 2019 Nov 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101614637 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-6074 (Electronic) Linking ISSN: 23266066 NLM ISO Abbreviation: Cancer Immunol Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, [2013]- |
| مواضيع طبية MeSH: | Antineoplastic Agents, Immunological/*pharmacology , Breast Neoplasms/*immunology , Breast Neoplasms/*therapy , CD47 Antigen/*antagonists & inhibitors , Immunoglobulin A/*immunology , Neutrophils/*immunology , Receptors, Immunologic/*antagonists & inhibitors, Animals ; Antibodies, Monoclonal/pharmacology ; Antibody-Dependent Cell Cytotoxicity/immunology ; Antigens, Differentiation/immunology ; Breast Neoplasms/pathology ; CD47 Antigen/immunology ; Cell Line, Tumor ; ErbB Receptors/antagonists & inhibitors ; Female ; Humans ; Immunotherapy/methods ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Phagocytosis/drug effects ; Phagocytosis/immunology ; Receptor, ErbB-2/antagonists & inhibitors ; Receptors, Immunologic/immunology ; Xenograft Model Antitumor Assays |
| مستخلص: | Therapeutic monoclonal antibodies (mAb), directed toward either tumor antigens or inhibitory checkpoints on immune cells, are effective in cancer therapy. Increasing evidence suggests that the therapeutic efficacy of these tumor antigen-targeting mAbs is mediated-at least partially-by myeloid effector cells, which are controlled by the innate immune-checkpoint interaction between CD47 and SIRPα. We and others have previously demonstrated that inhibiting CD47-SIRPα interactions can substantially potentiate antibody-dependent cellular phagocytosis and cytotoxicity of tumor cells by IgG antibodies both in vivo and in vitro IgA antibodies are superior in killing cancer cells by neutrophils compared with IgG antibodies with the same variable regions, but the impact of CD47-SIRPα on IgA-mediated killing has not been investigated. Here, we show that checkpoint inhibition of CD47-SIRPα interactions further enhances destruction of IgA antibody-opsonized cancer cells by human neutrophils. This was shown for multiple tumor types and IgA antibodies against different antigens, i.e., HER2/neu and EGFR. Consequently, combining IgA antibodies against HER2/neu or EGFR with SIRPα inhibition proved to be effective in eradicating cancer cells in vivo In a syngeneic in vivo model, the eradication of cancer cells was predominantly mediated by granulocytes, which were actively recruited to the tumor site by SIRPα blockade. We conclude that IgA-mediated tumor cell destruction can be further enhanced by CD47-SIRPα checkpoint inhibition. These findings provide a basis for targeting CD47-SIRPα interactions in combination with IgA therapeutic antibodies to improve their potential clinical efficacy in tumor patients. (©2019 American Association for Cancer Research.) |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antigens, Differentiation) 0 (Antineoplastic Agents, Immunological) 0 (CD47 Antigen) 0 (CD47 protein, human) 0 (Immunoglobulin A) 0 (Receptors, Immunologic) 0 (SIRPA protein, human) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ERBB2 protein, human) EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (Receptor, ErbB-2) |
| تواريخ الأحداث: | Date Created: 20191107 Date Completed: 20201001 Latest Revision: 20201001 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1158/2326-6066.CIR-19-0144 |
| PMID: | 31690649 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2326-6074 |
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| DOI: | 10.1158/2326-6066.CIR-19-0144 |