Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies

Rebecca Adams; Gabriel Osborn; Bipashna Mukhia; Roman Laddach; Zena Willsmore; Alicia Chenoweth; Jenny L C Geh; Alastair D MacKenzie Ross; Ciaran Healy; Linda Barber; Sophia Tsoka; Victoria Sanz-Moreno; Katie Elizabeth Lacy; Sophia N Karagiannis

doi:10.1080/2162402X.2022.2127284

Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies

Rebecca Adams, Gabriel Osborn, Bipashna Mukhia, Roman Laddach, Zena Willsmore, Alicia Chenoweth, Jenny L C Geh, Alastair D MacKenzie Ross, Ciaran Healy, Linda Barber, Sophia Tsoka, Victoria Sanz-Moreno, Katie Elizabeth Lacy, Sophia N Karagiannis

St. John's Institute of Dermatology
School of Basic & Medical Biosciences
Informatics Department
Breast Cancer Now
School of Cancer and Pharmaceutical Sciences
The Plastic Surgery Department, Guy's and St Thomas Hospital, London, United Kingdom.
King's College and St Thomas' Hospitals
1Department of Hepatology, Imperial College London, London, UK. 2Institute of Liver Studies at King's College School of Medicine at King's College Hospital, London, UK. 3Institute of Human Health and Performance, University College London, London, UK. 4Department of Asthma Allergy and Lung Biology, King's College London, London, UK. 5Division of Critical Care Medicine, University of Alberta, Edmonton, Canada.

Research output: Contribution to journal › Review article › peer-review

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Abstract

The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.

Original language	English
Article number	2127284
Number of pages	17
Journal	OncoImmunology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1080/2162402X.2022.2127284
Publication status	Published - 3 Oct 2022

Keywords

checkpoint inhibitors
Fc receptors
immunotherapy
macrophages
melanoma
monoclonal antibodies
polarization
tumor microenvironment

UN SDGs

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

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10.1080/2162402X.2022.2127284

Adams et al OncoImmunology 2022Final published version, 6.06 MBLicence: CC BY

Cite this

Adams, R., Osborn, G., Mukhia, B., Laddach, R., Willsmore, Z., Chenoweth, A., Geh, J. L. C., MacKenzie Ross, A. D., Healy, C., Barber, L., Tsoka, S., Sanz-Moreno, V., Lacy, K. E., & Karagiannis, S. N. (2022). Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies. OncoImmunology, 11(1), Article 2127284. https://doi.org/10.1080/2162402X.2022.2127284

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title = "Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies",

abstract = "The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.",

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author = "Rebecca Adams and Gabriel Osborn and Bipashna Mukhia and Roman Laddach and Zena Willsmore and Alicia Chenoweth and Geh, {Jenny L C} and {MacKenzie Ross}, {Alastair D} and Ciaran Healy and Linda Barber and Sophia Tsoka and Victoria Sanz-Moreno and Lacy, {Katie Elizabeth} and Karagiannis, {Sophia N}",

note = "Funding Information: The authors acknowledge support by the Medical Research Council (MR/L023091/1), (MR/V049445/1); Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London (C604/A25135); CR UK//NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); Breast Cancer Now (147; KCL-BCN-Q3); the Guy{\textquoteright}s and St Thomas{\textquoteright} Foundation Trust Charity Melanoma Special Fund (SPF573); Cancer Research UK (C30122/A11527; C30122/A15774). The research was supported by the National Institute for Health Research Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London (IS-BRC-1215-20006). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.",

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doi = "10.1080/2162402X.2022.2127284",

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AU - Osborn, Gabriel

AU - Mukhia, Bipashna

AU - Laddach, Roman

AU - Willsmore, Zena

AU - Chenoweth, Alicia

AU - Geh, Jenny L C

AU - MacKenzie Ross, Alastair D

AU - Healy, Ciaran

AU - Barber, Linda

AU - Tsoka, Sophia

AU - Sanz-Moreno, Victoria

AU - Lacy, Katie Elizabeth

AU - Karagiannis, Sophia N

N1 - Funding Information: The authors acknowledge support by the Medical Research Council (MR/L023091/1), (MR/V049445/1); Cancer Research UK King’s Health Partners Centre at King’s College London (C604/A25135); CR UK//NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587); Breast Cancer Now (147; KCL-BCN-Q3); the Guy’s and St Thomas’ Foundation Trust Charity Melanoma Special Fund (SPF573); Cancer Research UK (C30122/A11527; C30122/A15774). The research was supported by the National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London (IS-BRC-1215-20006). The authors are solely responsible for study design, data collection, analysis, decision to publish, and preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2022/10/3

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N2 - The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.

AB - The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.

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JO - OncoImmunology

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ER -

Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies

Abstract

Keywords

UN SDGs

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