Worldwide Cancer Research Menu

Like molecular clockwork – how biological timers control the immune system

Professor Philip Hodgkin, based in Australia, is using funding from Worldwide Cancer Research to work out the molecular ‘clockwork’ behind biological timers that control how the immune system responds once it is activated. His team are particularly interested in looking at genes that keep these timers ticking that are also involved in lymphoma. They hope that their approach will reveal more about how the normal immune response works so that they can identify what is going wrong when lymphoma develops.

Finding new treatments for Non-Hodgkin’s Lymphoma

Cancer drugs known as histone deacetylase (HDAC) inhibitors, that work by blocking the action of a molecule called histone deacetylase, have recently been approved for the treatment of some lymphomas. Dr Zelent has evidence that they may also be effective treatments for other lymphomas including Non-Hodgkin's Lymphoma. He is now using his Worldwide Cancer Research grant to investigate exactly how a specific type of HDAC called HDAC9 is involved in Non-Hodgkin's Lymphoma and to investigate if HDAC inhibitors could also be given to these patients.

Investigating Mantle Cell Lymphoma

Mantle cell lymphoma is a rare type of Non-Hodgkin's Lymphoma (cancer of the lymphatic system - part of our immune system) and its causes are still unknown. It is mostly found in middle aged to older individuals (60-65 years) and is more common in men than women. The median survival for mantle cell lymphoma is only 3-5 years and sadly the vast majority of patients cannot be cured. However, there are a small number of patients who have a stable form of the disease and do not need treatment for long periods of time. With her Worldwide Cancer Research grant Dr Beà is analysing samples from mantle cell lymphoma patients (aggressive and the more stable forms) to identify which alterations are responsible for the disease and to understand the genetic reasons for this difference in how patients respond to the disease.

Researching a therapy for the rare disease Enteropathy-Associated T-cell Lymphoma

Enteropathy-associated T-cell lymphoma (EATL) is a very rare type of T-cell lymphoma.  It usually occurs in the small intestine, and is associated with celiac disease. It occurs in a small number of patients who do not respond to a gluten-free diet, the standard treatment for celiac disease, and who therefore suffer from chronic inflammation in their intestines. Patients having a massive increase in faulty, premalignant, white blood cells in their small intestine are at high risk for developing EATL. EATL is a fast-growing (aggressive) lymphoma and the future for these patients is not very good with an average five year survival of only 10-20%.  New and better treatments are therefore urgently needed.Together with his colleagues, Dr Jeroen van Bergen has discovered a small group of cells in the intestines that he believes could be key to the initiation of EATL.  He is therefore using his grant to study how these begin to grow and divide rapidly, whilst avoiding death.  Finally the team will look for chemicals or biological inhibitors that could stop these rogue cells from dividing and cause them to die.  He hopes that his findings could provide important information to aid the treatment of EATL in the future.

Studying the role of B-cell receptors in human lymphomas

B-cells are a type of white blood cell that is a part of our immune system. The majority of the B-cells live within specific areas of different organs such as lymph nodes, which are located throughout the body, or the spleen, which is found near our stomach. These organs, called lymphoid tissues, also form part of the lymphatic system, and this is where our bodies fight many of the infections that we experience. Cancers that affect B-cells, such as lymphomas, often grow in the lymph nodes or spleen, but they can be found anywhere in the lymphatic system. B cells have a key molecule on their surface, called the B-cell receptor (BCR), which allows them to recognise specific structures, called antigens, which can, for example, be found on viruses or bacteria. When B cells recognise an antigen, they become activated, making them able to detect and fight infections. Many cancers that affect B-cells are also thought to depend on the BCR to grow and survive. Some mutations, which cause the BCR to be switched on, have been found in a small group of non-Hodgkin's lymphoma cases. Professor Packham and his team have found a new way in which the BCR maybe be able to be switched on, even without the antigen, and this may play a role in nearly all cases of follicular lymphoma, a disease that develops in lymphoid tissues. If the BCR is switched on without antigen, it may allow these cancer cells to gain supporting signals from cells within the surrounding area. They believe that this may be a cause for the growth or survival of lymphomas, and aim to study this further with their new grant. This research will provide new information about human lymphomas, which could be used to improve the way we treat this disease, and possibly find new treatment options.

Developing a Vaccine for the Epstein-Barr Virus

With the recent success of the cervical cancer vaccine which protects against the HPV virus, scientists are turning their attention to other cancer-causing viruses such as the Epstein-Barr virus (EBV). Professor Christian Münz is already making progress. Using a specially developed mouse model, he is looking at different ways of trying to activate the immune system into fighting EBV.EBV is a very common herpes virus which most of us carry our entire lives without any problems. However for some the virus can trigger cancer. EBV is thought to cause up to 200,000 cases of cancer worldwide every year, including Hodgkin’s lymphoma, nose and throat cancer, and stomach cancer.*

With the help of an earlier Worldwide Cancer Research grant, Professor Münz has already found two specific types of molecule which can prime the immune system for EBV attack. He and his lab now want to build on this success and will use his latest grant to try and find a third potential vaccine component, one which trains a special type of white blood cell (called a killer T-cell) to find and destroy EBV infected cells.

After this, the next step is to develop a vaccine ‘prototype’ by mixing all three vaccine components in a specially developed formulation, and then test this formulation against EBV in the mouse model.

* Statistics from Cancer Research UK Press Release (March 2014).

Dissecting the Myc signalling pathway, a driver of lymphoma growth

Dr Arianna Sabo' is investigating the role of Myc in lymphomas.  Myc is a protein that sticks to DNA.  It can regulate thousands of genes, thereby controlling key cellular processes, such as cell growth, division and death. It is not difficult to imagine that when the amount of Myc in a cell is not carefully controlled, such as in cancer cells where it is frequently excessively high, it can lead to aberrant behaviors, such as unconstrained cell growth and proliferation.

Dr Sabo' told us “We are aiming to identifying critical downstream genes regulated by Myc that are selectively activated in cancer cells opposed to normal cells.  These genes will thereby provide us with new therapeutic targets for the elimination of Myc-driven tumours whilst unharming healthy cells.”

Understanding how marginal-zone lymphomas start

Lymphomas are cancers of white blood cells, the two main forms being Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma.  Dr Jose A. Martinez-Climent is investigating a form of lymphoma called marginal zone lymphomas which are a group of slow growing Non-Hodgkin’s Lymphomas, often diagnosed in people in their sixties and accounting for 10% of all human lymphomas.

There are three types of marginal zone lymphomas and a better understanding of the mechanisms involved will allow a better diagnosis of these different subtypes as well as helping to tailor therapies.

Dr Martinez-Climent explained “We have found that the molecule NKX2-3 is present at high levels in a third of marginal zone lymphomas and appears to be involved in allowing the cancer cells to spread and form secondary tumours in lymph tissue. They are now using a mouse model of the disease and samples from patients to more fully analyse the role of NKX2-3 in marginal zone lymphomas.”

He concluded “We expect that these studies will help pave the way to develop novel therapeutic approaches targeting NKX2-3 in marginal-zone lymphomas.”