IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

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

doi:10.3390/cancers12113376

IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

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

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Abstract

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.

Original language	English
Article number	3376
Pages (from-to)	1-19
Number of pages	19
Journal	Cancers
Volume	12
Issue number	11
DOIs	https://doi.org/10.3390/cancers12113376
Publication status	Published - 15 Nov 2020

Keywords

AllergoOncology
Cancer
Cancer immunotherapy
Cross-linking
Cytotoxicity
FcεRI
IgE
Monocytes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Nakamura et al Cancers 2020Final published version, 3.57 MBLicence: CC BY
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Nakamura, M., Souri, E. A., Osborn, G., Laddach, R., Chauhan, J., Stavraka, C., Lombardi, S., Black, A., Khiabany, A., Khair, D. O., Figini, M., Winship, A., Ghosh, S., Montes, A., Spicer, J. F., Bax, H. J., Josephs, D. H., Lacy, K. E., Tsoka, S., & Karagiannis, S. N. (2020). IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype. Cancers, 12(11), 1-19. Article 3376. https://doi.org/10.3390/cancers12113376

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title = "IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype",

abstract = "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.",

keywords = "AllergoOncology, Cancer, Cancer immunotherapy, Cross-linking, Cytotoxicity, FcεRI, IgE, Monocytes",

author = "Mano Nakamura and Souri, {Elmira Amiri} and Gabriel Osborn and Roman Laddach and Jitesh Chauhan and Chara Stavraka and Sara Lombardi and Anna Black and Atousa Khiabany and Khair, {Duaa O} and Mariangela Figini and Anna Winship and Sharmistha Ghosh and Ana Montes and Spicer, {James F} and Bax, {Heather J} and Josephs, {Debra H} and Lacy, {Katie E} and Sophia Tsoka and Karagiannis, {Sophia N}",

year = "2020",

month = nov,

day = "15",

doi = "10.3390/cancers12113376",

language = "English",

volume = "12",

pages = "1--19",

journal = "Cancers",

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Nakamura, M , Souri, EA , Osborn, G , Laddach, R, Chauhan, J, Stavraka, C , Lombardi, S, Black, A, Khiabany, A, Khair, DO, Figini, M, Winship, A, Ghosh, S, Montes, A, Spicer, JF , Bax, HJ , Josephs, DH, Lacy, KE, Tsoka, S & Karagiannis, SN 2020, 'IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype', Cancers, vol. 12, no. 11, 3376, pp. 1-19. https://doi.org/10.3390/cancers12113376

TY - JOUR

T1 - IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

AU - Nakamura, Mano

AU - Souri, Elmira Amiri

AU - Osborn, Gabriel

AU - Laddach, Roman

AU - Chauhan, Jitesh

AU - Stavraka, Chara

AU - Lombardi, Sara

AU - Black, Anna

AU - Khiabany, Atousa

AU - Khair, Duaa O

AU - Figini, Mariangela

AU - Winship, Anna

AU - Ghosh, Sharmistha

AU - Montes, Ana

AU - Spicer, James F

AU - Bax, Heather J

AU - Josephs, Debra H

AU - Lacy, Katie E

AU - Tsoka, Sophia

AU - Karagiannis, Sophia N

PY - 2020/11/15

Y1 - 2020/11/15

N2 - 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.

AB - 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.

KW - AllergoOncology

KW - Cancer

KW - Cancer immunotherapy

KW - Cross-linking

KW - Cytotoxicity

KW - FcεRI

KW - IgE

KW - Monocytes

UR - http://www.scopus.com/inward/record.url?scp=85096137304&partnerID=8YFLogxK

U2 - 10.3390/cancers12113376

DO - 10.3390/cancers12113376

M3 - Article

C2 - 33203088

SN - 2072-6694

VL - 12

SP - 1

EP - 19

JO - Cancers

JF - Cancers

IS - 11

M1 - 3376

ER -

IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

Abstract

Keywords

UN SDGs

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