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Tumour-associated macrophage polarisation and re-education with immunotherapy
Debra H. Josephs1,2,Heather J. Bax1,2,Sophia N. Karagiannis1,*
1
St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, Faculty of Life Sciences & Medicine, King’s College London
2
Research Oncology, Division of Cancer Studies, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Hospital, London, UK
DOI: 10.2741/E735 Volume 7 Issue 2, pp.334-351
Published: 01 January 2015
*Corresponding Author(s):  
Sophia N. Karagiannis
E-mail:  
sophia.karagiannis@kcl.ac.uk
Abstract

Monocytes/macrophages constitute important contributors of cancer-associated inflammation. Through their plasticity and capacity to become polarised by tumours towards less activatory and more immunosuppressive (M2) phenotypes, tumour-associated macrophages (TAM) are thought to support tumour progression. Orchestrated by T helper 2 (Th2)-biased stimuli, macrophage recruitment, activation and polarisation in tumour microenvironments is associated with poorer clinical outcomes. Their key roles in supporting tumour progression and their capacity for plasticity have focused targeted and immunotherapeutic strategies to counteract macrophage pro-tumourigenic activities and to re-ignite their tumour-cytotoxic power. Therapeutic approaches include blockade of macrophage recruitment into tumours, suppression of TAM survival, re-polarisation towards an M1-like phenotype and antibody therapies to enhance TAM anti-tumoural activities. Future immunotherapeutic directions may include monoclonal antibodies with enhanced effector functions. Antibodies of different classes, including those of the IgE class, shown to restrict tumour growth by harnessing monocyte/macrophage cytotoxic properties in pre-clinical cancer models, may synergise or re-educate these potent immune sentinels to destroy rather than support tumours. Opportunities for monitoring monocyte/macrophage polarisation or activatory signatures in patients may inform clinical management.

Key words
monocytes,macrophages,tumour immunotherapy,monoclonal antibodies,tumour microenvironment,M1 macrophages,M2 macrophages,Th1/Th2 responses,IgG,IgE,ADCC,ADCP
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Debra H. Josephs, Heather J. Bax, Sophia N. Karagiannis. Tumour-associated macrophage polarisation and re-education with immunotherapy. Frontiers in Bioscience-Elite. 2015. 7(2); 334-351.