Tumours are not just made of tumour cells. Tumours are surrounded by a variety of non-cancerous cells called stromal cells that include fibroblasts, immune cells, blood vessels and a dense extracellular matrix, which form what is known as the tumour stroma or the tumour microenvironment. In some tumours, the stroma can represent up to 80% of the tumour mass and is not a simple bystander. In fact, the tumour microenvironment can support tumour initiation, progression, metastasis and drug resistance. The stromal cells co-exist, co-evolve and interact with cancer cells in tumours.
How tumours become resistant to therapies? How tumours evade the immune system? And how tumours metastasize to other organs are vital questions that remain to be addressed. Drug resistance, tumour immunity and metastasis are all influenced by the complex tumour microenvironment. The overall goal of our research is to understand how cancer cells interact with the stromal cells and how these tumour-host interactions affect drug resistance, tumour progression/metastasis and the immune response to tumours, with the aim to find more effective therapies for aggressive cancers such as pancreatic cancer and metastatic breast cancer.
To address these important questions we are using a variety of cutting-edge and innovative technologies that we have established in the lab, including flow & mass cytometry, fluorescent multispectral tissue imaging, proteomics with primary tumours, bioinformatics, 3D in vitro tumour models, patient samples, and pre-clinical models and in vivo imaging.
– Dr Ainhoa Mielgo
The tumour microenvironment plays a key role in cancer initiation, progression, metastasis and drug resistance.
A macrophage is a specialised type of immune cell which primary function is to engulf any foreign substance (i.e. pathogens, cancer cells) in a process called phagocytosis.
Macrophages are found in all tissues. Macrophages can be tissue resident or can arise from circulating monocytes from blood vessels and differentiate into macrophages in the tissue. Besides phagocytosis, macrophages also stimulate the recruitment and activation of another type of immune cells called lymphocytes, and support wound healing and tissue repair. There are different subsets of macrophages that exert distinct and even sometime opposite functions. M1-like macrophages promote inflammation and activation of the immune system, while M2-like macrophages support tissue repair and suppress the immune system.
Macrophages are one of the most abundant cell types in the tumour microenvironment. Macrophages are among the first immune cells to infiltrate tumours. Cancer is associated with inflammation which results in the recruitment of circulating blood monocytes that give rise to TAMs (Tumour associated macrophages).
TAMs can secrete growth factors and enzymes that support tumour initiation, progression and metastasis. However, TAMs can also kill tumour cells. Hence, a better understanding of the pro-tumorigenic and anti-tumorigenic functions of TAMs could lead to the development of more effective anti-cancer therapies.
A fibroblast is a type of cell that is responsible for making the collagen and extracellular matrix required to maintain the structural integrity of all tissues in our body. Fibroblasts play an important role in wound healing. Following tissue injury, fibroblasts migrate to the site of damage, where they deposit new collagen and facilitate the healing process.
Tumours are like wounds that do not heal. In fact, cells that are involved in wound healing such as fibroblasts and macrophages play also an important role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression and represent a promising target for cancer therapies. Therefore, their structural and functional contributions to cancer are being intensively investigated.
The pancreas is a digestive and endocrine organ in the abdominal cavity behind the stomach. The pancreas secretes digestive enzymes that assist the digestion and absorption of nutrients. The pancreas also secretes essential hormones, including insulin and glucagon that regulate the blood sugar (glucose) levels in our body