IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype
IgE contributes to host-protective functions in parasitic and bacterial infections, often by monocyte and macrophage recruitment. We previously reported that monocytes contribute to tumour antigen-specific IgE-mediated tumour growth restriction in rodent models. Here, we investigate the impact of Ig...
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Format: | Article |
Language: | English |
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MDPI AG
2020-11-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/12/11/3376 |
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doaj-a43bc7ac15c04fcfba2107a385e34f2e |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mano Nakamura Elmira Amiri Souri Gabriel Osborn Roman Laddach Jitesh Chauhan Chara Stavraka Sara Lombardi Anna Black Atousa Khiabany Duaa O. Khair Mariangela Figini Anna Winship Sharmistha Ghosh Ana Montes James F. Spicer Heather J. Bax Debra H. Josephs Katie E. Lacy Sophia Tsoka Sophia N. Karagiannis |
spellingShingle |
Mano Nakamura Elmira Amiri Souri Gabriel Osborn Roman Laddach Jitesh Chauhan Chara Stavraka Sara Lombardi Anna Black Atousa Khiabany Duaa O. Khair Mariangela Figini Anna Winship Sharmistha Ghosh Ana Montes James F. Spicer Heather J. Bax Debra H. Josephs Katie E. Lacy Sophia Tsoka Sophia N. Karagiannis IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype Cancers IgE monocytes FcεRI cancer cancer immunotherapy AllergoOncology |
author_facet |
Mano Nakamura Elmira Amiri Souri Gabriel Osborn Roman Laddach Jitesh Chauhan Chara Stavraka Sara Lombardi Anna Black Atousa Khiabany Duaa O. Khair Mariangela Figini Anna Winship Sharmistha Ghosh Ana Montes James F. Spicer Heather J. Bax Debra H. Josephs Katie E. Lacy Sophia Tsoka Sophia N. Karagiannis |
author_sort |
Mano Nakamura |
title |
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype |
title_short |
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype |
title_full |
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype |
title_fullStr |
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype |
title_full_unstemmed |
IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype |
title_sort |
ige activates monocytes from cancer patients to acquire a pro-inflammatory phenotype |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2020-11-01 |
description |
IgE contributes to host-protective functions in parasitic and bacterial infections, often by monocyte and macrophage recruitment. We previously reported that monocytes contribute to tumour antigen-specific IgE-mediated tumour growth restriction in rodent models. Here, we investigate the impact of IgE stimulation on monocyte response, cellular signalling, secretory and tumour killing functions. IgE cross-linking on human monocytes with polyclonal antibodies to mimic formation of immune complexes induced upregulation of co-stimulatory (CD40, CD80, CD86), and reduced expression of regulatory (CD163, CD206, MerTK) monocyte markers. Cross-linking and tumour antigen-specific IgE antibody-dependent cellular cytotoxicity (ADCC) of cancer cells by cancer patient-derived monocytes triggered release of pro-inflammatory mediators (TNFα, MCP-1, IL-10, CXCL-10, IL-1β, IL-6, IL-23). High intratumoural gene expression of these mediators was associated with favourable five-year overall survival in ovarian cancer. IgE cross-linking of trimeric FcεRI on monocytes stimulated the phosphorylation of intracellular protein kinases widely reported to be downstream of mast cell and basophil tetrameric FcεRI signalling. These included recently-identified FcεRI pathway kinases Fgr, STAT5, Yes and Lck, which we now associate with monocytes. Overall, anti-tumour IgE can potentiate pro-inflammatory signals, and prime tumour cell killing by human monocytes. These findings will inform the development of IgE monoclonal antibody therapies for cancer. |
topic |
IgE monocytes FcεRI cancer cancer immunotherapy AllergoOncology |
url |
https://www.mdpi.com/2072-6694/12/11/3376 |
work_keys_str_mv |
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doaj-a43bc7ac15c04fcfba2107a385e34f2e2020-11-25T04:07:57ZengMDPI AGCancers2072-66942020-11-01123376337610.3390/cancers12113376IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory PhenotypeMano Nakamura0Elmira Amiri Souri1Gabriel Osborn2Roman Laddach3Jitesh Chauhan4Chara Stavraka5Sara Lombardi6Anna Black7Atousa Khiabany8Duaa O. Khair9Mariangela Figini10Anna Winship11Sharmistha Ghosh12Ana Montes13James F. Spicer14Heather J. Bax15Debra H. Josephs16Katie E. Lacy17Sophia Tsoka18Sophia N. Karagiannis19St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKDepartment of Informatics, Faculty of Natural & Mathematical Sciences, King’s College London, London WC2B 4BG, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKBiomarker Unit, Department of Applied Research and Technology Development, Fondazione, IRCCS Istituto Nazionale dei Tumouri Milano, 20133 Milan, ItalyDepartment of Medical Oncology and Clinical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UKDepartment of Medical Oncology and Clinical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UKDepartment of Medical Oncology and Clinical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UKSchool of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKDepartment of Informatics, Faculty of Natural & Mathematical Sciences, King’s College London, London WC2B 4BG, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London, Tower Wing, 9th Floor, Guy’s Hospital, London SE1 9RT, UKIgE contributes to host-protective functions in parasitic and bacterial infections, often by monocyte and macrophage recruitment. We previously reported that monocytes contribute to tumour antigen-specific IgE-mediated tumour growth restriction in rodent models. Here, we investigate the impact of IgE stimulation on monocyte response, cellular signalling, secretory and tumour killing functions. IgE cross-linking on human monocytes with polyclonal antibodies to mimic formation of immune complexes induced upregulation of co-stimulatory (CD40, CD80, CD86), and reduced expression of regulatory (CD163, CD206, MerTK) monocyte markers. Cross-linking and tumour antigen-specific IgE antibody-dependent cellular cytotoxicity (ADCC) of cancer cells by cancer patient-derived monocytes triggered release of pro-inflammatory mediators (TNFα, MCP-1, IL-10, CXCL-10, IL-1β, IL-6, IL-23). High intratumoural gene expression of these mediators was associated with favourable five-year overall survival in ovarian cancer. IgE cross-linking of trimeric FcεRI on monocytes stimulated the phosphorylation of intracellular protein kinases widely reported to be downstream of mast cell and basophil tetrameric FcεRI signalling. These included recently-identified FcεRI pathway kinases Fgr, STAT5, Yes and Lck, which we now associate with monocytes. Overall, anti-tumour IgE can potentiate pro-inflammatory signals, and prime tumour cell killing by human monocytes. These findings will inform the development of IgE monoclonal antibody therapies for cancer.https://www.mdpi.com/2072-6694/12/11/3376IgEmonocytesFcεRIcancercancer immunotherapyAllergoOncology |