The Tumour Microenvironment

Tumours are not just made of tumour cells. Tumours are surrounded by a variety of non-cancerous cells that include cells from the immune system, fibroblasts, cells from the vasculature and extracellular matrix, which form what is known as the tumour stroma or the tumour microenvironment.

Solid cancers such as pancreatic and breast cancer have a rich tumour microenvironment that affects cancer progression, metastasis and resistance to treatments.

The tumour microenvironment plays a key role in cancer initiation, progression and metastasis.

– Dr Ainhoa Mielgo
Principal Investigator
The Tumour Microenvironment

The Tumour Microenvironment

Frequently Asked Questions

What is a macrophage?

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.

What is the role of macrophages in cancer?

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.

What is a fibroblast?

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.

What is the role of fibroblasts in cancer?

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.

What is the function of the pancreas?

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

Selected Publications

    • Ireland L, Santos A, Campbell F, Figueiredo C, Hammond D, Ellies L, Weyer-Czernilofsky U, Bogenrieder T, Schmid M, Mielgo A. Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer. Oncogene, January 2018
    • Ireland L, Santos A, Ahmed MS, Rainer C, Nielsen SR, Quaranta V, Weyer-Czernilofsky U, Engle DD, Perez-Mancera P, Coupland SE, Taktak AF, Bogenrieder T, Tuveson DA, Campbell F, Schmid MC, Mielgo A. Chemoresistance in pancreatic cancer is driven by stroma-derived insulin-like growth factors. Cancer Research, October 2016.
    • Sebastian Nielsen, Valeria Quaranta, Andrea Linford, Perpetua Emeagi, Carolyn Rainer, Almudena Santos, Lucy Ireland, Takao Sakai, Keiko Sakai, Yong-Sam Kim, Dannielle Engle, Fiona Campbell, Daniel Palmer, Jeong Heon Ko, David Tuveson, Emilio Hirsch, Ainhoa Mielgo, and Michael Schmid. Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nature Cell Biology, March 2016.
    • Sunil Advani, Maria Fernanda Camargo, Laetitia Seguin, Ainhoa Mielgo , Sudarshan Anand , Angel Hicks , Joseph Aguilera, Aleksandra Franovic, Sara Weis and David Cheresh. Kinase-independent role for CRAF drives tumor radioresistance via CHK2. Nature Communications, 2015. Sep 3;6:8154.
    • Laetitia Seguin, Shumei Kato, Aleksandra Franovic, M. Fernanda Camargo, Jacqueline Lesperance, Kathryn C. Elliott, Mayra Yebra, Ainhoa Mielgo, Andrew M. Lowy, Hatim Husain, Tina Cascone, Lixia Diao, Jing Wang, Ignacio I. Wistuba, John V. Heymach, Scott M. Lippman, Jay S. Desgrosellier, Sudarshan Anand, Sara M. Weis, David A. Cheresh. An integrin β3–KRAS–RalB complex drives tumour stemness and resistance to EGFR inhibition. Nature Cell Biology. 2014. May;16(5):457-68.
    • Ainhoa Mielgo, Laetitia Seguin, Miller Huang, Fernanda Camargo, Sudarshan Anand, Aleksandra Franovic, Sara Weis, Sunil Advani, Eric Murphy, David A. Cheresh. A MEK-independent role for CRAF in mitosis and tumor progression. Nature Medicine, Nov 2011 13; 17(12):1641-5.
    • Ainhoa Mielgo, Vicente A. Torres, Kiran Clair and Dwayne G. Stupack. Paclitaxel promotes a caspase 8-mediated apoptosis via death effector domain association with microtubules. Oncogene, October 2009; 8;28(40):3551-62.
    • Ainhoa Mielgo*, Wolf Wrasidlo*, Vicente A. Torres, Simone Barbero, Konstantin Stoletov, Takashi L. Suyama, Richard L. Klemke, William H. Gerwick, Dennis A. Carson and Dwayne G. Stupack. The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8. Proc. Natl. Acad. Sci, 2008 February; 105(7): 2313-8. A.M and W.W contributed equally to this work.

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