Mucosal Immunity and Cancer Laboratory

Our research focus

Function of intestinal immune cells in bowel cancer

Intraepithelial lymphocytes (IELs) are immune cells which continually survey intestinal epithelial cells for infection or damage. Bowel cancer forms when the epithelial cells become damaged and change, growing in an uncontrolled manner. The role of IELs in this process, and whether or not they play a role in tumour cell growth or killing tumour cells, has not been studied in detail. Our laboratory aims to understand these cells, including the molecules that regulate their function in steady state development and in the development of cancer. 

Regulation of cytokines in the gastrointestinal tract

Cytokines, such as IL-17 and IL-22, are secreted by immune cells and are critical in boosting epithelial cell and tumour survival in the intestine. Bowel cancer patients with increased IL-17 and IL-22 levels experience increased tumour growth and have a poorer prognosis. We are dissecting the molecular pathways and cell types involved in regulating IL-17 and IL-22 production to investigate the role these cytokines play in bowel cancer progression. It is crucial that we understand these mechanisms so we can develop new immune cell-mediated therapies to treat gastrointestinal cancers.

Influence of the microbiome on immune health  

Each person’s microbiome is unique and is made up of good bacteria, viruses and fungi which live on the body’s surfaces, such as the skin and intestine. Our understanding of these resident microbes and how they affect the body’s immune response to an infectious organism or disease, such as cancer, is limited. We are working to understand the mechanisms which link the microbiome to overall immune cell health, including the activation of transcription factors that guide immune cell development, as well as the cytokines they secrete in order to communicate with the rest of the body’s cells.

Fast facts

As well as being found in the blood, immune cells are also in the body’s tissues, which they continuously survey for infection and cancer.

Mucus-covered tissues including the lungs and gastrointestinal tract. These sites are home to specialised immune cells, which play a critical role in maintaining mucosal surfaces in order to protect the body from the external environment.

All the bacteria and other microbes that live on the body’s surfaces, such as the skin and intestine. Interaction between these microbes and immune cells is critical in shaping the immune system, and can even influence the body’s response to some cancer treatments.

Recent publications

Trends in Immunology

Control of Lymphocyte Fate, Infection, and Tumor Immunity by TCF-1.
DOI: 10.1016/j.it.2019.10.006.

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Journal of Experimental Medicine

TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis.

DOI: 10.1084/jem.20181778

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Journal of Experimental Medicine

Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation.

DOI: 10.1084/jem.20121588

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Our team

Meet our researchers

  • Dr Lisa Mielke - Head, Mucosal Immunology Laboratory Publications
  • Pavitha Parathan - Research Assistant
  • Dinesh Raghu - Postdoctoral Research Fellow Publications
  • Kelly Tran - Research Assistant


Tumour Immunology Laboratory

Our research focus

We constantly use and develop cutting-edge methodologies, including multiplex immuno-fluorescence and RNA-Scope for the characterisation of the tumour microenvironment, protein arrays for the detection of cancer-specific antibodies, and in vitro T cell assays for the detection of novel immunogenic peptides, among others. We are exploring how a successful immune recognition is orchestrated and translated from the early (innate arm) to the late (adaptive) response.

This ‘immunostaging’ of cancers will allow us to understand why and how immunotherapy works for some patients but not for others, and how we can increase the number of patients who benefit from these treatments. The laboratory has extensive experience in clinical trial monitoring and collaborative industry projects, all centred on improving outcomes and quality of life for cancer patients. We collaborate with several leading cancer research laboratories in Australia and internationally.

Fast facts

Tumour cells often look very different to the immune system when compared to healthy cells. To avoid destruction, tumours use a variety of strategies to overcome or to ‘hide’ from an immune response. This interaction of tumour cells with a large variety of immune cells can be more or less pronounced and influence outcome of the disease or response to particular treatments. The quality and quantity of these interactions can be measured on multiple levels, which all together represent the tumour-immune engagement.

Antibodies are proteins produced by a subtype of immune cells which can specifically recognise, bind and often neutralise antigens which the immune system recognises as foreign or a threat (e.g. viruses or bacteria). In cancer, specific antibodies are produced as a response to antigens on cancer cells, which are different than those on normal cells. While their function in the immune recognition of cancer is unclear, their detection in the blood indicates the presence of cancer cells.

Recent publications

Science

Characterising the phenotypic evolution of circulating tumour cells during treatment.
Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells

DOI: 10.1126/science.aay5516

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Frontiers in Immunology

Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette-Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma.

DOI: 10.3389/fimmu.2018.00411

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Nature Communication

Characterising the phenotypic evolution of circulating tumour cells during treatment.

DOI: 10.1038/s41467-018-03725-8

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Our team

Meet our researchers


Cancer and Inflammation Laboratory

Our research focus

We focus our research on three approaches to interfere with the communication between cancer and normal cells within a tumour.

Stat3 and tumourigenesis

Pronounced epithelial Stat3 activity is not only observed during wound-healing, but also in a majority of cancers including those in the colon, stomach, breast and lung. Our lab recently established a novel link, showing that the cytokine interleukin (IL)-11 – through its shared gp130 receptor, the associated Jak kinases and Stat3 signaling – promotes tumourigenesis. Surprisingly, this signaling cascade also becomes rate limiting for the growth of colon and gastric tumours that are driven by mutations in well recognised cancer pathways.

Neoplastic cells

We are therapeutically exploiting that neoplastic cells have often developed a higher dependency on a particular signal than their normal counterparts. For instance, oncogenic activation of the WNT/beta-catenin signaling cascade is the most common tumour-initiating event that occurs in epithelial stem cells and results in the development of sporadic colorectal cancer. Because interference with the gp130/Stat3 signaling cascades limits the expansion of such intestinal (cancer) stem cells, the addiction of colon cancer cells to gp130/Stat3 signaling can be therapeutically exploited in these tumours where targeting of the mutated WNT/beta-catenin signaling cascade is not feasible.

Hck activation

The cellular composition of the tumour microenvironment affects how well a tumour can grow and respond to targeted and immune-modulatory therapy. Although these processes are affected by many different cell types within the tumour stroma, macrophages and other myeloid-derived cells are among the most important players. We have found that the myeloid cell kinase Hck is highly abundant in the tumour microenvironment and aberrant Hck activation suppresses an effective anti-tumour immune response. We are therefore identifying ways by which we can most effectively target Hck to restore and augment anti-tumour immune responses to more effectively kill the cancer cells.

Fast facts

Cancer cells have hijacked for their own benefit the inflammatory processes that help support wound-healing of normal tissues.

Within the tumour there are a number of cell types, both cancer cells and non-cancer cell types. This collective of different cell types is characterised by many molecular interactions that collectively determine how well a tumour responds to treatment.

A gene or protein which is identified to cause, or play a major role, in the disease.

A drug which attacks a specific protein of the cancer. Such drugs therefore only work on cancer where such a protein confers a specific benefit for a particular cancer to grow and spread.

Recent publications

Cancer Cell

Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cells-Mediated Colon Cancer Progression.

DOI: 10.1016/j.ccell.2017.03.006

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Nature Communications

IL33-mediated mast cell activation promotes gastric cancer through macrophage mobilization.

DOI: 10.1038/s41467-019-10676-1 (2019)

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Nature Reviews Cancer

Therapeutically exploiting STAT3 activity in cancer – using tissue repair as a road map.

DOI: 10.1038/s41568-018-0090-8 (2019)

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Our team

Meet our researchers

  • Prof Matthias Ernst - Director, ONJCRI | Head, Cancer And Inflammation Program |
    Head, Cancer And Inflammation Laboratory | Head, School Of Cancer Medicine, La Trobe University Publications
  • Shoukat Afshar-Sterle - Research Assistant Publications
  • Amr Allam - Postdoctoral Research Fellow Publications
  • Mariah Alorro - PhD Student
  • David Baloyan - Flow Cytometry Operator Publications
  • Christine Dijkstra - Research Assistant
  • Belinda Duscio - Research Assistant
  • Moritz Eissmann - Victorian Cancer Agency Research Fellow Publications
  • Gangadhara Gangadhara - Postdoctoral Research Fellow Publications

  • Anne Huber - PhD Student
  • Jennifer Huynh - Postdoctoral Research Fellow Publications
  • Saumya Jacob (Parambate) - Research Assistant
  • Riley Morrow - PhD Student
  • Megan O'Brien - Research Assistant
  • Lokmand Pang - PhD Student
  • Ashleigh Poh - Postdoctoral Research Fellow Publications
  • Angela Sanchez Hormigo – Scientist Publications