Aula Ammar

Aula Ammar

Project Title: 

The role of macrophage in breast cancer and melanoma progression and treatment response

Host Organisation: 

Department of Oncology, The University of Nottingham

Short biography

I got my Bsc in Pharmacy from Tishreen University, Syria in 2001. Then I attended a postgraduate course in laboratory diagnostics in Damascus University, Syria before I was appointed as a teacher assistant at Tishreen University (2003-2004).

I did my PhD with the Translational & Radiation Biology Research Group, department of Oncology, University of Nottingham. During my PhD I worked in a project investigating the molecular characteristics of tumour-associated lymphendothelium and their role in cancer metastasis to lymph nodes. Later on, I joined the Tumour Biology Group at UCL London working with animal models of colorectal cancer and looking at the effect of the tumour microenvironment on the distribution of potential therapeutic antibodies.

Upon returning to Syria, I worked as a lecturer of different subjects including modern molecular techniques, cell and molecular biology, biotechnology and biochemistry at the School of Pharmacy, Tishreen University and also at Al-Andalus University for Medical Sciences.

The CASCADE fellowship has increased my expertise in cancer and radiation biology. I now have a postdoc position at the University of Glasgow working in a related area, investigating the role of inflammatory cytokines in ovarian cancer. 

Brief description of research project

This work aimed to understand how macrophages, a type of white blood cell that infiltrates into tumours, might contribute to breast cancer progression and response to radiotherapy. Macrophages are plastic cells that can change their phenotype and function according to the environment they are in at any given time. We assessed the density of macrophage infiltration by looking at total macrophages (CD68 positive cells) as well as the density of CD163 positive cells, a sub-population of macrophages usually known as type 2 or M2 macrophages. Results showed that breast cancer infiltration with CD163 positive macrophage associate with shorter survival in breast cancer patients and is usually higher in oestrogen receptor negative cases. We also investigated the tumoural expression of cytokines associated with macrophages (e.g., IL-6, IL-10, TNF-a, CCL17, CCL17 and CCR4) however they were not directly involved in regulating lymphovascular invasion or lymph node metastasis. Interestingly, patients expressing high tumoural IL-6, IL-10 or tumours positive for
CCR4 showed prolonged survival and good prognosis.

The second focus of the study was to understand how different types of macrophages may alter breast cancer response to radiotherapy. Luminal and Basal /triple negative breast cancers respond differently to radiotherapy with basal/triple negative group showing more resistance and higher local recurrence rates. Luminal and basal/triple negative models of breast cancer cell lines were treated with supernatants collected from different types of donor harvested and matured macrophages (M1 and M2 macrophages) with or without radiation. Our results showed that different macrophage treatments have different effects on breast cancer cell proliferation and response to therapy. Interestingly, a specific type of macrophages known as mature M1 was associated with increased resistance to radiotherapy in the basal/triple negative breast cancer cell line but did not alter luminal cell response to radiotherapy. Understanding the mechanisms of radioresistance induced by macrophages may reveal new targets for basal/triple negative breast cancer and therefore improve patient survival.