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Tumour Microenvironment and Cancer Signalling Group

Group overview

One of the major goals in cancer research today is to map cancer heterogeneity. Cancer heterogeneity is not only based on the genetic makeup of cancer cells, but also on their versatile responses to a hostile environment in which they have to compete to survive and thrive. There is a network of complex and dynamic communications occuring between cancer cells and the surrounding microenvironment, including the local and infiltrating immune cells.

Cancer cells have developed strategies to shape the tumour microenvironment into an entity that complies with their needs; access to nutrients and evasion of detection by the immune system. Making things worse, these adaptions often also make cancer cells more aggressive, leading to the formation of secondary tumours at distant sites (metastases) and greater resistance to our current arsenal of anti-cancer drugs and therapies.

The Tumour Microenvironment and Cancer Signalling Group seeks to redress this imbalance by turning the tumour microenvironment from fertile to barren for cancer cells.

A better understanding of the intricate interactions between cancer cells and their surroundings will ultimately deliver better treatments and therapies for patients. Dr Michael Buchert, Head, Tumour Microenvironment and Cancer Signalling Group
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Our focus

DCLK1

DCLK1 is a microtubule-associated protein that catalyses the polymerisation of tubulin dimers. This process is critical in the formation of microtubules, a major component of the cellular cytosekeleton, and also important in many cellular functions such as cell division and migration. DCLK1 expression is excessively upregulated in various types of cancer and, pertinently, high DCLK1 expression is significantly correlated with poorly differentiated cancers, lymph node metastasis, advanced clinical stage, and poorer overall patient survival, suggesting that the overexpression of DCLK1 may accelerate cancer development.

Tuft cells

Tuft cells are a morphologically unique cell type, best characterized by striking microvilli that form an apical tuft. These cells represent approximately 0.5% of tissue epithelial cells depending on location. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may thus make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions. Our lab is using powerful single-cell sequencing approaches and has developed experimentally tractable tools in order to interrogate this rare cell population, with the aim of unraveling its physiological importance in inflammation-driven gastrointestinal diseases, such as colon and gastric cancers.

Innate lymphoid cells

Innate lymphoid cells (ILCs) are a newly discovered type of innate immune cell which resemble lymphocytes but lack a T cell receptor. These cells are predominantly found  in mucosal surfaces associated with epithelial tissues, such as the gut, lung and skin, and have important roles in immunity, infection and homeostasis. Our lab is investigating the crosstalk between Tuft cells and ILC2 cells during gastric homeostasis and cancer.

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Quick facts

What is the tumour microenvironment?

The tumour microenvironment (TME) is the cellular environment within which the tumour exists. This includes the surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules and the extracellular matrix (ECM).

What are Tuft cells?

Tuft cells are rare chemosensory cells scattered throughout the epithelium tissue of the digestive tract. Their biological functions include tissue repair and regeneration, as well as modulation of immune responses during parasite infections. Tuft cell numbers increase during the early stages of tumour development; the importance of this increase is not yet well understood.

What are ILC2 cells?

ILC2s play the crucial role of secreting type 2 cytokines in response to certain parasitic infections. They have also been implicated in the development of allergic lung inflammation. They express characteristic surface markers and receptors for chemokines, which are involved in distributing lymphoid cells to specific organ sites. ILC2s are critical in primary responses to local Th2 antigens, such as helminths and viruses, and this is why ILC2s are abundant in tissues of the skin, lungs, liver and gut. Their role in cancer development is not yet well understood.

What is EMT?

The epithelial–mesenchymal transition (EMT) is a process through which epithelial cells lose their cell polarity and intercellular adhesion, instead gaining migratory and invasive properties to become mesenchymal stem cells, which are multipotent stromal cells that can differentiate into a variety of different cell types.

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