Macrophages in ovarian cancer and their interactions with monoclonal antibody therapies

Author:

Osborn Gabriel1,Stavraka Chara123ORCID,Adams Rebecca1,Sayasneh Ahmad4,Ghosh Sharmistha2,Montes Ana2,Lacy Katie E1,Kristeleit Rebecca2,Spicer James3,Josephs Debra H123,Arnold James N3,Karagiannis Sophia N15

Affiliation:

1. St. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London , London , United Kingdom

2. Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust , Great Maze Pond, London , United Kingdom

3. School of Cancer and Pharmaceutical Sciences, King’s College London , London , United Kingdom

4. Department of Gynecological Oncology, Surgical Oncology Directorate, Guy’s and St Thomas’ NHS Foundation Trust, School of Life Course Sciences, King’s College London , London , United Kingdom

5. Breast Cancer Now Research Unit, School of Cancer and Pharmaceutical Sciences, King’s College London, Guy’s Cancer Centre , London , United Kingdom

Abstract

Abstract The unmet clinical need for effective treatments in ovarian cancer has yet to be addressed using monoclonal antibodies (mAbs), which have largely failed to overcome tumour-associated immunosuppression, restrict cancer growth, and significantly improve survival. In recent years, experimental mAb design has moved away from solely targeting ovarian tumours and instead sought to modulate the wider tumour microenvironment (TME). Tumour-associated macrophages (TAMs) may represent an attractive therapeutic target for mAbs in ovarian cancer due to their high abundance and close proximity to tumour cells and their active involvement in facilitating several pro-tumoural processes. Moreover, the expression of several antibody crystallisable fragment (Fc) receptors and broad phenotypic plasticity of TAMs provide opportunities to modulate TAM polarisation using mAbs to promote anti-tumoural phenotypes. In this review, we discuss the role of TAMs in ovarian cancer TME and the emerging strategies to target the contributions of these cells in tumour progression through the rationale design of mAbs.

Funder

Cancer Research UK

National Institute for Health Research

NIHR in England

DoH for Scotland, Wales

Northern Ireland Experimental Cancer Medicine Centre

Guy’s and St Thomas’s Foundation Trust Charity Melanoma Special Fund

Breast Cancer Now

Cancer Research UK King’s Health Partners Centre at King’s College London

Medical Research Council

Cancer Research Institute/ Wade F.B. Thompson CLIP

NIHR Biomedical Research Centre

Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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