Speaker Abstract RCMM 2017: Professor Dr. Seow Heng Fong
Are macrophages in the tumour microenvironment useful targets for development of cancer therapeutics?
Iris Goh Wen Li1, Norhafizah Mohtarrudin1, Mohd Faisal Jabar2 and Seow Heng Fong1
1Department of Pathology, 2Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.
The tumour microenvironment consists of a complex network of cells including myeloid and lymphoid, fibroblastic and endothelial cells as well as vascular and lymphatic vessels. The dynamic interactions between the tumour cells and surrounding stroma and the secretion of growth factors and cytokines contribute to tumour development and progression. Factors that influence tumour progression and metastasis include alterations in the extracellular matrix composition, activation of surrounding cells, and phenotype of immune cells. In general, tumour infiltration with macrophages with M2-phenotype promote tumour progression whereas infiltration of memory cytotoxic and Th1 T lymphocytes are often associated with good prognosis. A number of strategies to target the macrophages have been used. These strategies include the killing of macrophages or reducing their recruitment into the tumour site or polarizing M2-like to M1-like macrophages. Tumour growth has been shown to be reduced by trabectin that directly kills macrophages or by blockade with anti-CSF1R. Inhibiting CCL2 has also been shown to inhibit macrophage recruitment.
The aim of our study was to determine whether IFN-γ + LPS THP-1 macrophages (M1-like) can repolarize to IL-4 (M2-like) macrophages in response to conditioned media (CM) from TW06 (a nasopharyngeal carcinoma cell line) tumorspheres or alter their cytokine secretion pattern. The macrophages were characterised by the cytokines expressed and surface markers. Tumorspheres were characterised by the expression of surface CD44+CD24–EpCAM+. The cytokines secreted in response to TW06 tumoursphere CM were measured by using a cytokine antibody array.
Higher expression of CCL2, CCL3, CCL5 and CXCL1 from M2-like macrophages were found to be consistent with the pro-tumour activity of M2-like macrophages. CXCL10 detected in M1-like macrophages may contribute to the anti-tumour and angiostatic effects of M1-like macrophages.
The pattern of chemokines secreted from macrophages in response to conditioned media from TW06 tumourspheres were consistent with their pro-tumour and anti-tumour activity.