Cytokine and Cancer Signalling Group

Our research focus

Gastrointestinal Cancer models

With the advancement of immunotherapies, new cancer models are needed that mimic both the tumour cells as well as the normal body cells present in cancer tissues to test the effectiveness of therapies. We develop novel murine cancer models by establishing organoids, 3-D miniature organ-like structures, from gastric and colorectal cancers tissues. These organoids represent new models enabling the testing of genetic variation in the tumour cells or the tumour microenvironment selectively and the testing of new immunotherapies.

Cytokine signalling

Cytokines are signalling molecules that mediate the crosstalk between cancer cells and the normal cells within cancerous tissue. Depending on the source of the cytokine and the responding cell type, the impact can either be tumour promoting or tumour inhibitory. We are studying, two cytokine signalling pathways, IL33/ST2 and IL6/IL11/STAT3. Both are highly active in gastro-intestinal cancers and generate an immunosuppressive microenvironment. We study how they promote primary tumour growth, metastasis formation and responses to (immuno)therapies.

Immunotherapy

Immunotherapies are drugs that manipulate the body’s own immune cells to attack cancers. One class of immunotherapies, the immune checkpoint inhibitors, has strongly improved therapy outcomes for many different cancer types. However, in gastric and colorectal cancer only a minority of patients respond to these therapies. We study the role of cytokine signalling in the anti-tumour responses to immune checkpoint blockade. Additionally, we investigate, if inhibition of these cytokine signalling pathways can improve the efficacy of immunotherapies against gastric and colorectal cancers.

Recent publications

ScienceDirect

Generation of gene-of-interest knockouts in murine organoids using CRISPR-Cas9

DOI: 10.1016/j.xpro.2023.102076

17 March 2023

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Frontiers

IL33 and Mast Cells-The Key Regulators of Immune Responses in Gastrointestinal Cancers?

DOI: 10.3389/fimmu.2020.01389

3 July 2020

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Nature

IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization

DOI: 10.1038/s41467-019-10676-1

21 June 2019

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Our team

Meet our researchers

  • Dr Moritz Eissmann - Head, Cytokine and Cancer Signalling Group Publications
  • Amr Allam - Postdoctoral Research Fellow
  • Anne Huber – Postdoctoral Research Fellow
  • Saumya Jacob – Research Assistant
  • Josh Konecnik – Research Assistant

Tumour Microenvironment and Cancer Signaling Group

Our research focus

DCLK1

DCLK1 is a microtubule-associated protein which catalyses the polymerisation of tubulin dimers. This process is critical in the formation of microtubules, a major component of the cellular cytoskeleton, 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

A structurally unique cell type, best characterised by striking microvilli which 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 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 unravelling its physiological importance in inflammation-driven gastrointestinal diseases, such as colon and gastric cancers.

Innate lymphoid cells

These cells are a newly discovered type of innate immune cell which resemble lymphocytes but lack a T cell receptor. They 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 interplay between Tuft cells and ILC2 cells during gastric homeostasis and cancer.

Fast facts

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

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.

They play a 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 is why they are abundant in tissues of the skin, lungs, liver and gut. Their role in cancer development is not yet well understood.

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.

Recent publications

Nature Communications

A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development

DOI: 10.1038/s41467-023-42215-4

28 October 2023

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Biomedicines

Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis

DOI: 110.3390/biomedicines11030990

22 March 2023

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Frontiers

Crosstalk between epithelium, myeloid and innate lymphoid cells during gut homeostasis and disease

DOI: 10.3389/fimmu.2022.944982

16 September 2022

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Our team

Meet our researchers

  • Birhanu Ayelign Jemere - PhD Student
  • Birhanu Jemere - PhD Student
  • Kiruthiga Raghunathan - PhD Student
  • Rokaya Rehouma - PhD Student
  • Chloe Raes - International Intern