Bringing oncology and immunology together

An understanding of immunology is critical to cancer research. The Lydia Becker Institute of Immunology and Inflammation at Manchester brings together medical oncologists and basic researchers in cancer immunology to expedite our understanding. Institute Director Professor Tracy Hussell discusses the important link between immunology and cancer, and why Manchester is the perfect place to lead on research that could lead to better patient outcomes.

Immunology underpins the majority of human disease, but it is complicated. It is therefore essential that experts are included from across the scientific spectrum, from basic science through to clinical studies, at every stage of the journey to advise and progress.

Immune pathways do not happen in isolation. For example, the latest treatment strategy for cancer involves unleashing the activity of immune cells using ‘checkpoint inhibitors'. However, unleashing immunity may not make it active; it might just enable it to be activated. An understanding of immunity can provide combined options to push the immune cell into activity.  

The best questions are often the simplest ones. Instead of delving around at the molecular level, it might be better to pan out and ask: 'Why is this organ healthy whereas another is not?' It might also be better to look for things that are missing from the healthy state rather than trying to reduce excesses in disease.

As an example, we recently published a study that is relevant to a type of cancer, basal cell carcinoma. The dominant feature of this is an excess of the basal cell type, one of the innermost cells of the deeper epidermis of the skin. The simple question to ask is: 'What normally stops basal cells from increasing in number?' Our investigations showed that basal cells divide when they recognise dying cells. If dying cells are present all the time, then basal cells keep going. One solution therefore is to block the ability of basal cells to recognise dying cells.

There are many clinical diseases where we have been using the same treatments for a long time, despite efforts to find something better or safer. One of the stumbling blocks in the development of new treatments is that we tend to view the processes of disease as abnormal when they may actually be normal processes that haven't received the communication to stop. We need to change attitudes as to what disease is. Fibrosis, for example, is a normal part of the repair process, but it becomes a significant problem if it doesn't stop.

Professor Tracy Hussell

Tracy Hussell is Director of the Lydia Becker Institute of Immunology and Inflammation at The University of Manchester and Director of the Manchester Collaborative Centre for Inflammation Research (MCCIR), a collaboration with industry in blue-sky inflammation research.

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Cancer and immunology

Our understanding of immunology's vital role in research discovery has continued to expand, and one area of particular importance in our understanding of the immune system is its interaction with tissue structure and composition.

Cells within an organ are guided along conduits and only stop when they encounter something of interest. Appropriate positioning of immune cells is critical for effective function. If immune cells do not stop in a cancer, then they won't be able to engage with cancer cells and kill them.

To understand this better requires the immunology, matrix biology and cancer sciences to unite better, and that is something we are achieving at Manchester. We also need to learn from other disciplines. The way a mother's immune system ignores the growing foetus in pregnancy is, in some ways, not too dissimilar from the ability of cancer to avoid the immune system. At The Lydia Becker Institute, we share patient samples in vivo models. This leads to faster, joined-up science.

A good multidisciplinary team should be seamless. The Institute contains the necessary blend of clinicians and basic scientists – we're all part of the same team, working on the same grant applications and papers.

Increasing collaborations

The number of collaborations is rising fast. Our immunologists are now working in the areas of prostate, ovarian and lung cancers, as well as the toxicities common in radiotherapy.

Radiation can cause an inflammatory complication in some patients that limits the window in which they can be treated. Understanding the nature of this toxicity will allow us to develop approaches to limit it. With the raft of immune-targeted therapies currently available, it is likely that the cure is already out there.

Our immunologists are part of a mobile lung-screening study that is trying to minimise the numbers of people who undergo unnecessary surgery. Patients who attend screening provide a nasal blot. The proteins captured by this are analysed by mass spectrometry and scrutinised for a 'signature' that we hope will differentiate between those who have early cancer and those who do not.

If a protein signature can be detected, then this research will enable the development of a self-test kit that people can use at home. It's incredible that Manchester provides the environment that allows a basic scientist such as me to address something so close to the clinic; it really is incredible that we can move so seamlessly between specialisms and experts.

A good scientist

Someone recently asked me what I thought made a good scientist. I said: "If there's a big red button in the middle of the room with a sign saying 'don't press', a good scientist will press it to see what happens."

I tell PhD students that this is the only time when you are paid to do your hobby, but you may spend a long time doing experiments to work out what the question is! You have to be energetic, inquisitive and questioning. I'm fortunate to be surrounded by people with those attributes and the patients who are willing to contribute.

The future

The future for the Lydia Becker Institute is everywhere, but immediately we need to work with health data scientists to understand the extent of patients with multiple chronic diseases.

You'll rarely find a patient with one disease. So we need to understand patient disease complexity and then reverse translate that back into the laboratory. Only then can we ask relevant fundamental immunology questions in the right setting.