News archive

November 18, 2025

Researchers at the University of Southampton will investigate whether weight loss and diabetes medications such as Ozempic could help boost the effectiveness of immunotherapy.

They are undertaking a new research project to better understand why breast cancer is less responsive to treatment and more likely to spread in women with obesity.

The new project has received £243,000 from Against Breast Cancer to carry out the research over the next three years.

Women with obesity who develop breast cancer have a worse prognosis. They don’t respond as well to treatments, including antibody therapy, which has been very effective in patients of a healthy weight.

Now researchers at Southampton’s Centre for Cancer Immunology are investigating why this is the case and what can be done to make antibody treatments more effective in these patients.

Researchers will be using a newly developed 3D ‘mini-tumour’ research model that includes human breast cancer cells, fat cells, immune cells, and supporting tissue. It’s the first to closely replicate the inflamed, fatty tumour environment found in obesity within a lab.

As the model can’t fully replicate all aspects of breast cancer, researchers will also use mice on a high-fat diet to test a range of interventions.

A scientist wearing a blue lab coat branded “Against Breast Cancer” and blue gloves uses a pipette at a laboratory bench. Shelves of bottles and equipment are on the wall beside him, and boxes of lab supplies are arranged on the bench.

Dr Charlie Birts, a lecturer in antibody therapeutics at the University of Southampton, is leading the research. He says: “In obesity, we often see that a lot of immune cells find it harder to get into the tumour, and when they do, they don’t work as well as they should. We think the extra fat tissue that's surrounding the tumour is changing the nutrients that are available and increases the amount of inflammation, creating an inhospitable environment that makes it harder for immune cells to fight the cancer.”

In women with obesity, breast cancer is more likely to spread to other parts of the body, such as the bones, the lungs and the liver, leading to a higher likelihood of poorer outcomes.

Preliminary data shows that when the tumour is growing in the breast it can start to ‘prime’ other sites in the body – creating a favourable environment for the cancer to spread to and grow. Part of the project will be looking at the mechanisms behind this spread and how obesity influences it.

Previous observational studies have shown that diabetic breast cancer patients taking metformin tend to have better overall outcomes than those not receiving the drug, and this may be particularly relevant in patients with obesity.

An exciting aspect of the project will look at how metformin and GLP-1 agonists (the wider scientific term for drugs like Ozempic and Mounjaro) that regulate the metabolism could be used in combination with antibody therapies to slow tumour growth.

Dr Birts commented: “These drugs have already been shown to be safe and are widely used in clinical practice. If we can show that combining these medications with antibody therapy improves the effectiveness of treatment, it could improve outcomes for breast cancer patients across a range of body weights.”

“Against Breast Cancer are delighted to fund this exciting new study,” said Dr Mark Powell, Research Manager at Against Breast Cancer. “Gaining a deeper understanding on why obesity increases the risk of secondary breast cancer and how diabetes and inflammation play a role could pave the way to tailored treatments and better outcomes for breast cancer patients.”

Against Breast Cancer’s mission is to fund research that prevents loss of life from secondary breast cancer, the leading cause of breast cancer deaths. This new Fellowship led by Dr Birts, complements our existing ABC Discover and ABC Therapeutic Antibody programmes, which are funded for five- and ten-years, respectively.

May 27, 2025

Breast cancer researchers from the University of Southampton will marshal and support walkers at a charity event in Hampshire in aid of the research they conduct.

The Breast Walk Ever, on Sunday 8 June, is in aid of Against Breast Cancer (ABC), which funds research into secondary breast cancer, including several PhD researchers at the University of Southampton.

ABC-funded PhD student Grace Hayes, who is researching bone metastasis from breast cancer, will be marshalling at the event for the third year running – and for the second year alongside her mum Deborah Parnell.

Deborah, from Southampton, lost her aunt, Mary Wilson, back in 1975 when she was just 52. Mary had breast cancer, which had spread to her bones.

“Mum always told me lots about my great auntie Mary when I was growing up, and losing her to breast cancer had a real impact on my mum,” said Grace.

“She always remembers the pain her aunt was in. We’re both inspired to support Against Breast Cancer to remember my great aunt, but also because breast cancer is so prevalent and the research is making such great strides.”

Groundbreaking research funded by ABC at the University of Southampton is contributing to developing a blood test to detect 12 types of cancer.

The miONCO test measures genetic regulators in our bodies that are vital for controlling processes such as growth and development.

Grace, who works at the University’s Centre for Cancer Immunology, said: “Myself and colleagues feel it’s so important to help at Breast Walk Ever. Not only does it give us the opportunity to thank ABC for supporting and funding our research, but it allows us to meet and chat with fundraisers so they can hear directly where their donations are going and how grateful we are for their efforts.”

Researchers from the University of Southampton joining Grace on 12 May include Dr Charlie Birts, Lecturer and Researcher in Antibody Therapeutics funded by ABC, ABC-funded research technician Anna-Liese Silber, and Professor of Immunology and Immunotherapy Stephen Beers.

Richard Martin, ABC’s Events Manager, said: It's great to be back in Hampshire for a third year this June. We cannot wait to meet all our wonderful supporters at the finish. We even have pink ice cream for them this year!”

May 1, 2025

Cancer scientists say they have engineered a new type of super-strong antibody which could be used to boost the immune systems of patients fighting the disease.

Experts from the University of Southampton altered the shape and flexibility of the tiny proteins, which are naturally produced by white blood cells to protect the body from bacteria and viruses.

They discovered that their antibody prototype, which was more rigid, was able to trigger a stronger response from the immune system compared to those made by our bodies.

Their study, which was funded by Cancer Research UK, has been published in the journal Nature Communications.

Professor Mark Cragg , from the Centre for Cancer Immunology at the University of Southampton, said: "The concept of using immuno-stimulation for cancer treatment is very exciting.

“Our study confirms that making even subtle increases in the rigidity of antibodies significantly stimulates immune activity, creating a powerful immune response against the disease.

“This approach works for multiple antibodies targeting different immune receptors.

“The ability to engineer these rigid antibodies could help develop more potent drugs that can stimulate the immune system to target cancer or other diseases.”

The Y-shaped antibodies fight infections by targeting and then binding onto molecules on the surface of bacteria and viruses, or even cancerous cells.

They can also be engineered to attach to receptors on immune cells to activate our body’s immune defences.

But not all antibodies do this effectively, said study co-author Isabel Elliott , a PhD student from Southampton.

She added: “The shape and flexibility of antibodies is crucial for how well they can activate immune cells – and we found more rigid antibodies seem to be better at this.

“The reason for this is likely because these rigid antibodies can hold molecules on the immune cells closer together, which triggers a stronger activation signal.

“Floppier antibodies are less likely to do this effectively.”

The two arms of antibodies, which give its Y shape, are linked by a series of bridges, named disulfide bonds.

The Southampton scientists managed to add extra bridges between the microscopic arms of the antibodies and tested it against standard variants.

Dr Ivo Tews , a Professor in Structural Biology at Southampton, added: “We used a supercomputer to visualise the structure of the antibody in atomic detail, allowing us to position extra disulfide bonds in the modified antibody.

“The results showed that the experiment worked and that the new, more rigid antibodies were more effective at activating immune cells.

“This idea of controlling antibody activity by making them more rigid seems to apply to many other similar molecules on immune cells.”

Executive Director of Research and Innovation at Cancer Research UK Dr Iain Foulkes , said: “Refining our understanding of how to enable our immune systems to fight cancer is a complex but fundamental step in helping cancer patients to have the best chance of a good outcome when receiving immunotherapy treatment.

“Using the latest technologies to engineer this type of super-strong antibody that could trigger a promising immune response will empower us to continue pioneering new ways to outsmart cancer.”

June 11, 2024

Research at the University of Southampton into new treatments for cancer has been given a boost thanks to a donation from the Hampshire and the Isle of Wight Royal Arch Freemasons.

The donation of £42,000 was made to the Cancer Immunology Fund which supports research at the Centre for Cancer Immunology, the UK’s first centre dedicated to cancer immunology research.

The funds were officially presented at the Royal Arch Province’s Annual Meeting, which was attended by 300 people.

Katherine de Retuerto received the donation on behalf of the University and gave a presentation explaining the work taking place at the Centre.

She said: “The University of Southampton has been the grateful recipient of immense generosity from the Freemasons over the years, and we really do appreciate their wonderful support.  We will use 100% of the donations directly to develop better, kinder, more effective cancer treatments to enable people to live longer and live better.”

The funds were raised through the Royal Arch Freemasons Annual Charity Appeal, with one member Gerry Underwood, giving a substantial sum, which helped the fundraising efforts get underway.

Commenting on the funds raised, their Head, Steve Allum, said: “Our members support towards this vital work will have a significant impact.”

May 21, 2024

Mark Cragg is Professor of Professor in Experimental Cancer Biology and is internationally recognised for his work in using the body’s own immune system to fight cancer.

His research analyses how the immune system interacts with cancer cells and how it can be harnessed with immunotherapy drugs called monoclonal antibodies. These drugs recognise and find specific proteins on cancer or immune cells and can then remove the cancer in different ways. Some attach to the cancer cells, making it easier for the cells of the immune system to find and destroy them, others block proteins that stop the immune system working (checkpoint inhibitors) and others bind to and stimulate the immune cells directly (immunostimulatory antibodies). Southampton has a rich and successful history in this area of cancer research bringing new antibody treatments from the laboratory to the clinic.

Mark is a member of the Antibody and Vaccine Group at the University of Southampton, joint Deputy Head of School Research in Cancer Sciences and is Director of the MRC DTP Translational Biomedical Sciences.

He is the only University of Southampton member of staff in the 2024 cohort of Fellows, who have been recognised for their remarkable contributions to advancing biomedical and health sciences, ground-breaking research discoveries and translating developments into benefits for patients and wider society.

Professor Cragg said: “I am surprised, delighted and honoured to have been elected a Fellow of the Academy of Medical Sciences, which is welcome recognition of the work we are doing in Centre for Cancer immunology. Awards like this are only possible through long-term commitment to a research area and collaboration with many different scientists, clinicians and industry colleagues. It recognises a rich history of Antibody Immunotherapy first developed in Southampton by George Stevenson and Martin Glennie and is only possible through the support from my fantastic colleagues within the Antibody and Vaccine Group. I am also grateful to my colleagues and collaborators across the University and beyond who I have worked with to take new antibody drugs into patients. This fellowship reflects the strength of cancer immunology translational research in Southampton. I look forward to working with the Academy to further the advances of Cancer Immunotherapy in the future”

The expertise of Fellows elected this year spans a wide range of clinical and non-clinical disciplines, from midwifery to cancer stem cell biology. They join an esteemed Fellowship of over 1,400 researchers who are at the heart of the Academy's work, which includes nurturing the next generation of researchers and shaping research and health policy in the UK and worldwide.

Professor Andrew Morris PMedSci, President of the Academy of Medical Sciences, said: “It is an honour to welcome these brilliant minds to our Fellowship. Our new Fellows lead pioneering work in biomedical research and are driving remarkable improvements in healthcare. We look forward to working with them, and learning from them, in our quest to foster an open and progressive research environment that improves the health of people everywhere through excellence in medical science.”

The new Fellows will be formally admitted to the Academy at a ceremony on Wednesday 18 September 2024.

The Academy of Medical Sciences is the independent, expert body representing the diversity of medical science in the UK. Its mission is to advance biomedical and health research and its translation into benefits for society. The Academy's elected Fellows are the most influential scientists in the UK and worldwide, drawn from the NHS, academia, industry and the public service.

March 15, 2024

Researchers in the Faculty of Medicine are to start a new study into how the immune system can prevent a common oesophageal cancer.

Adenocarcinomas are cancers that develop in gland cells which make mucus in the lining of the oesophagus. This is the most common type of oesophageal cancer in the UK and is linked to smoking, being overweight and having a long history of acid reflux. Oesophageal adenocarcinomas mainly affect the lower part of the oesophagus.

Eosinophils are a type of white blood cell and an important part of our body’s response to fighting illness and disease. They are often the first cells to respond when cancer starts to form within the body, they boost the immune systems defences and help control a tumours progression.

Funded by Cancer Research UK, Matthew Rose-Zerilli, Lecturer in Integrative Cancer Biology, will lead a new study analysing the potent activity of eosinophils in the early stages of oesophageal adenocarcinoma to better understand how the eosinophils can be better utilised to prevent cancer.

The multidisciplinary team will include scientists and clinicians from across Medicine at the University of Southampton (Drs Swindle, Rajak, Eren and Professor Underwood) and the University of Oxford University (Dr Boccellato).

Matthew said: “Our research will provide the first critical data to advance our understanding of how innate immunity can be directed to maintain epithelial barrier function, target pre-malignant cells and protect against development of oesophageal adenocarcinoma.”

March 13, 2024

Schoolchildren in Italy have made a virtual visit to the Centre for Cancer Immunology.

The class at Borgo Veneto Primary School in Padova met with Dr Giorgia Chiodin and other members of the Forconi Lab and tissue bank via video link. They were shown around the lab and have the opportunity to ask questions about what it’s like being a scientist. Giorgia also performed experiments and explained the research she is currently working on.

The event takes place each year to mark International Women and Girls in Science Day. It started in 2020 when one of Giorgia’s friends, Martina Moro, a teacher and left in the picture with the children, said her children had come across the job of a scientist.

Giorgia explained: “They were curious about the scientific and research world, so we organised our first videocall, thinking it would have been nice to show them some of the tools we had in the lab and explain in simple terms what kind of research we do. The event was received very well from the pupils and their school so we now arrange the call each year.

The school director and teachers are very grateful for this connection, and we are very happy to take part. It gives us the opportunity to bring together members of different teams to share research and showcase our work at the University, possibly encouraging little children to approach a career in science tomorrow.”

This year, the Mayor of Borgo Veneto also took part to the call showing his support to the initiative, which is very educational for the children, and unique in the Borgo Veneto area.

February 28, 2024

Cancer researchers from the University of Southampton have come together to celebrate the achievements of Professor Freda Stevenson, who has retired after a career in cancer research of more than 50 years.

Professor Stevenson first joined Southampton in 1970 and established the Tenovus Research Laboratory, alongside Professor George Stevenson. Her main research area focused on the immunobiology of B-cell diseases, with a particular focus on the immunoglobulin (Ig) receptor that is expressed at the cell surface on B-cells. Professor Stevenson was the first to design genetic vaccines to target this molecule, and these approaches are now deployed internationally across a range of tumours.

She also focused on the analysis of the genetics of this receptor, providing seminal insights into the classification of leukaemia and lymphoma using this approach. One of her papers , published in Blood in 1999 has now been cited more than 2,500 times. It describes how Ig gene status can classify patients with chronic lymphocytic leukaemia (CLL) into two major subsets each with very different clinical behaviour.

This work is the foundation of the current treatment paradigm for CLL and influences international approaches to clinical diagnostics and therapy.

Professor Stevenson spend some time in the NHS from 1980, at the Regional Immunology Centre in Southampton, which was founded to bring haematology-based science into the health service.  There, she was able to create her own research team before returning to the University and being made a Professor in 1997.

“I stayed in Southampton because we watched over the creation and growth of research into lymphoid tumors which culminated in the building of the Centre of Cancer Immunology,” she explained.  “Southampton now has a national and international reputation for cancer immunology of which we can all be proud.”

“The rate of progress in the field has been dramatic and I have remained part of it, with personal achievements, as well as contributions to REF and to research impact. With support from the University, I have been fortunate in having a slow handover of my involvement to others, especially Professor Francesco Forconi, and I remain as an advisor even after retirement.”

Over the years, her work has been recognised by several international research and clinical bodies, clearly demonstrating the value the global community places on Freda’s work. In 2014, the European Haematology Association awarded Freda the ‘Jean Bernard Life Time Achievement Award’ for contributions to the advancement of haematology.  A year later, she was awarded the Rai-Binet Medal by the International Workshop on CLL. In 2018, Professor Stevenson was awarded the Henry M Stratton Medal by The American Society of Hematology for her pioneering work on the biology of B-cell malignancies. In 2020, she was awarded a LifeTime Achievement Award by the British Society of Haematology.

Colleagues across Cancer Sciences at the University of Southampton have paid tribute to Professor Stevenson’s dedication to the field of cancer immunology.

Professor Francesco Forconi worked with Professor Stevenson on a number of studies and is now leading her lab. He said: “Freda’s contribution to the field of cancer immunology is widely celebrated and respected throughout the world. For me, on a personal level, she has inspired and guided me throughout the early stages of my research career and beyond. Freda taught me before time that studying the antigen-receptor and how it functions would explain how tumour cells exploit our body and how I should precisely treat B cell cancers. Her pioneering vision is now applied in [my] current clinical practice and, as a mature haematologist, I can prescribe targeted chemotherapy-free interventions, that can eradicate those B cell cancers, to all my patients. Her work, fostered by rigorous independent thinking, has heavily influenced my scientific views and that of my group to grow.

“I will carry on developing her founding studies on how lymphoma cells programme their environmental interactions for growth and survival, so that we will offer novel diagnostic, prognostic and therapeutic approaches in the most common lymphomas to that international scientific and clinical community to which Freda has successfully exposed us for many years. I take great pride in continuing her work at the University of Southampton.”

Professor Diana Eccles, Dean of the Faculty of Medicine at the University of Southampton, said: “Freda has been an inspirational and influential force in Southampton’s history of discovery science. Her major contributions to the study of cancer immunology have substantially altered our understanding of haematological malignancies and contributed to fundamental therapeutic advances. She has inspired many generations of scientists working in her lab as PhD students, post docs and colleagues and her influence and reach has been recognised internationally by the award of a number of prestigious prizes.”

Professor Jon Strefford, Head of Cancer Sciences in the Faculty of Medicine, said: “As the current Head of School of the School of Cancer Sciences (CS), I look forward to celebrating Professor Freda Stevenson’s career. Freda has had a truly remarkable academic career, with significant scientific and clinical impact, transforming our understanding of the most common form of leukaemia, and our approaches to its treatment.

“CS is enormously grateful to Freda for all she has contributed. Our school is currently in a strong position, with world-class academics leading internationally competitive research programmes, research that has benefited cancer patients. This strong position is, in no small part, built on the work that Freda did, delivered through her exceptional skill and ability that ultimately helped develop CS as a world-leader in the area of cancer immunology. Congratulations to Professor Stevenson for all her wonderful academic achievements.’

Professor Martin Glennie, now retired from the University, joined Professor Stevenson’s Southampton lab as a PhD student. He said: “Throughout her long and distinguished career Freda Stevenson has made Southampton Cancer Sciences a centre of international excellence for B-cell biology and shown how mechanistic understanding of cellular processes leads to advances in patient treatments.  She was the first person to show me, as a fresh faced PhD student, how rigorous laboratory experimentation was needed to test ideas and could lead to better understanding.”

Professor Peter Johnson added: “When I was thinking about coming to Southampton in 1998, cancer immunology was a long way from the mainstream of cancer research in the UK. But I had seen the fascinating work that Freda was doing on the lymphoma idiotype, and I knew this would be the ideal place to develop research at the interface between the laboratory and the clinic. Freda epitomises scientific rigour and complete commitment to the team around her, and she was instrumental in bringing both ideas and people to Southampton, through her international network of collaborators and admirers. Whenever I tell people I do cancer research in Southampton they ask after Freda: such is her profile. I am not sure how I am going to tell them she has retired.”

During her retirement, Professor Stevenson will be involved in international grant committees and with the top hematology journal, Blood.

February 2, 2024

A drug combination used to treat breast cancer, developed in collaboration with Centre for Cancer Immunology researchers, has shown to be well tolerated by patients and considerably improves response to treatment.

The Phase 1/2a trial, led by BioInvent International, is currently testing an exciting new FcgRIIB antibody (BI-1607) in combination with trastuzumab. The preliminary results, presented at the San Antonio Breast Cancer Symposium , covered 18 patients treated at doses ranging from 75 mg up to 900 mg flat dose of BI-1607. Treatment was well tolerated, and no serious adverse events related to BI-1607 were observed. Stable disease was observed in 6/11 evaluable patients who had previously progressed after trastuzumab treatment.

Southampton’s research, which led to the development of BI-1607 spans more than a decade.

Since working with BioInvent International from 2009, research  led by Professor Mark Cragg and Associate Professor Ali Roghanian from the Centre with Professor Björn Frendéus from BioInvent International, has showed an antibody called BI-1206 , targeted an immune receptor called FcgRIIB, and overcame resistance of certain blood cancer cells to treatment.

BI-1206 recruits immune cells toward the tumour and blocks the immune inhibition from FcgRIIB. Of note, when used in combination, BI-1206 overcomes some of the limitations of other anti-cancer therapeutic antibodies, such as rituximab, by stopping them being absorbed by the tumour cells.

Following this successful lab-based research, Professor Andrew Davies at the University of Southampton went on to conduct first in human trials of BI-1206 , funded by Blood Cancer UK and BioInvent International and sponsored by CRUK, to assess the maximum dose that could be given safely to humans alone and in combination with rituximab.

Ongoing clinical studies conducted by BioInvent International have evaluated BI-1206 in combination with rituximab for the treatment of Non-Hodgkin’s Lymphoma*.

Since then, the Southampton team alongside BioInvent, have demonstrated that targeting the inhibitory FcgRIIB can potentiate immunotherapy of solid tumours with a second FcgRIIB antibody, BI-1607 . Similar to BI-1206, BI-1607 is intended to enhance the efficacy and overcome resistance to existing cancer treatments such as trastuzumab**.

Professor Roghanian said: “Southampton has a rich history of taking lab-based research into the clinic and this demonstrates our commitment to help treat cancer patients. It is incredibly rewarding to see our research lead to important patient trials and then to see the positive results in those cancer patients who do not respond favourably to conventional treatments.”

Professor Cragg added: “This progress only comes from the long-standing collaboration with BioInvent, which now extends for over a decade. Taking new drugs and ideas into the clinic is difficult and having key partners is critical for us to do that.”

References

* https://www.bioinvent.com/en/clinical-programs/our-programs/bi-1206rituximab 

** https://www.bioinvent.com/en/clinical-programs/our-programs/bi-1607 

January 31, 2024

The Faculty of Medicine at the University of Southampton has launched a MSc Cancer Biology and Immunology course to meet the demands of the ever-changing landscape of cancer research.

With students expected to start this autumn, the new masters course will explore molecular and immunological approaches to the diagnoses, prevention and treatment of cancers.

Students will complete research and laboratory skills modules as well as an 18-week dissertation project alongside the University’s team of leading cancer experts, to equip them with the skills needed for careers in clinical and basic scientific research.

The course will draw on the University’s extensive expertise in biological sciences and cancer immunotherapy and students will have access to the Centre for Cancer Immunology, the UK’s first dedicated hub for cancer immunology research.

Emma Reeves, Programme co-lead, said: “The field of cancer research is changing every day and as an institution known around the world for our contribution to cancer research, we wanted to launch a new course that’s fit for training the leaders of the future. After an extensive review of the existing UK PGT market in the ‘Cancer’ and ‘Immunology’ themes, we opted for a holistic approach utilising our School wide expertise in cancer research, combining the fields of cancer biology and cancer immunology as the core theme of the programme.

"We have collaborated with current students to help us refine and maximise student experience and we are really looking forward to welcoming our first cohort in October."

January 17, 2024

In a new paper, several group leaders from the Centre for Cancer Immunology review and discuss the complicated mechanisms underlying anti-tumour immune responses, focusing on the potential of agonist antibodies to stimulate this and evoke cancer immunotherapy.

In the study entitled "Agonist antibodies for cancer immunotherapy: History, Hopes and Challenges" published in Clinical Cancer Research, our researchers offer valuable insights into the challenges, advancements, and future prospects of using these antibodies to harness the immune system to combat cancer.

They underscore the importance of understanding immune regulation for the successful development of antibody immunotherapy for cancer, emphasising the central role of costimulatory receptors in immune response modulation and discuss the challenges of developing agonist antibodies to target these receptors.

Isotype selection and affinity is paramount in designing effective agonist antibodies, as is the tumour microenvironment (TME) on the efficacy of agonist antibodies. Therefore, tailoring therapeutic strategies based on the TME composition, should be explored, say the researchers.

Despite challenges and modest clinical responses observed in early-phase trials to date, the researchers express optimism for the future of agonist antibodies.

Professors Mark Cragg, Sean Lim, Stephen Beers and Aymen Al-Shamkhani were involved in writing the paper.

December 13, 2023

Scientists at the Centre for Cancer Immunology have been involved in a new study, with researchers at the Universities of Liverpool and Aberdeen, which has gained new insight into a previously unknown aspect of the immune system that could help improve cancer treatment.

CTLA-4 is a cell surface molecule that plays a crucial role in the immune system. It is a so-called “checkpoint” receptor responsible for maintaining immune balance and tolerance and works to prevent the immune system becoming too active at the end of a normal immune response. However, it is also subverted by cancer cells to prevent the immune system from attacking them.

Therefore, scientists developed antibodies targeting CTLA-4 and these have shown promise in treating various cancers. However, the exact mechanisms behind their anti-tumour effects have remained elusive and there are issues with immune toxicity.

The new work sheds light on this and reveals there is also an overlooked form of CTLA4, that is released from the cell, known as soluble CTLA-4 (sCTLA-4). The research team investigated sCTLA-4’s potential impact on cancer immunotherapy and explored the functional properties of sCTLA-4 and tested the effectiveness of a specific antibody targeting sCTLA-4.

In the study, published in Molecular Therapy , they found that tumours expressing sCTLA-4 inhibited the activity of cytotoxic cancer-killing T-cells leading to the cancer growing and spreading more rapidly.

However, when the researchers blocked sCTLA-4 with a specific antibody, this suppression was reversed, and the T-cells were able to find and attack the cancer.

Professor Mark Cragg, from the University of Southampton, said: “This research, pioneered by Frank Ward and Lekh Dahal sheds new light on the previously unknown role of sCTLA-4 and emphasises the need for a comprehensive understanding of the various forms of immune checkpoint receptors. If we can better understand which forms are responsible for anti-tumour activity versus toxicity then it could allow us to provide a more nuanced, less toxic and effective approach to treatment.”

November 13, 2023

Scientists at the Centre for Cancer Immunology can pursue innovative ideas for cancer treatments thanks to the generosity of our supporters.

Three new research projects are being supported through the Cancer Immunology Fund, one of which is exclusively funded by a donation from the De Laszlo Foundation.

The funding – known as pump priming – provides vital support to researchers who have early concept ideas that need further investigation before more substantive funding from external sources can be secured. The three new ideas that the scientists are exploring are as follows:

Improving killer T cell function

Killer T cells are part of our immune system and identify cancer cells by detecting specific protein fragments (peptides) on the surface of cancer cells. The numbers of killer T cells at the site of the tumour have been linked with greater survival, however not all killer T cells within the tumour are able to recognise peptides.

The project funded by the De Laszlo Foundation, and led by Dr Emma Reeves, will mimic the T cell interaction with peptide fragments displayed on different types of cells within the tumour and give new insight into how killer T cells recognise cancer cells and whether other cells either help or prevent T cells from doing this.

Improving outcomes for oesophageal cancer patients

Oesophageal adenocarcinoma (EAC) is usually found in the lower oesophagus and sadly has a low survival rate. Research has shown that the majority of EAC is preventable through lifestyle changes and more effective screening. Additionally, research has shown that allergy can be protective against developing cancer and specificity for EAC, people with lots of a particular white blood cells called eosinophils, could be protected from developing cancer.

A project led by Dr Matthew Rose-Zerilli will study eosinophil cells in oesophagus tissue to understand how they can be manipulated to attack pre-cancerous cells and how they co-ordinate other immune cells capable of killing cancer. The long-term aim is to then understand how to combine eosinophil function with drugs, which have been shown to protect people from developing EAC.

Enhancing immune checkpoint treatments for lymphoma

Manipulation of the immune system using checkpoint treatments that "take the brakes off the immune system” has changed the way we treat different types of cancer such as melanoma and renal cancer. Unfortunately, these treatments have yielded disappointing results in several cancers of the lymph nodes (Lymphoma), likely reflecting the status of the immune system in these patients. Certain cells that make up the immune system can either help the Lymphoma grow or inhibit it. One of these cell types, macrophages, are present in large numbers in Lymphoma and influence whether treatments work effectively or not, but we do not know how or why.

Dr Jemma Longley will lead a project to better understand the interaction between macrophages and lymphoma cells. These macrophages can then be manipulated to stop them supporting the Lymphoma and instead help kill the tumour cells to improve the survival of patients with Lymphomas.

Professor Mark Cragg, Chair of the Cancer Immunology Fund Steering Committee, said: “We pride ourselves in fostering a curiosity-driven research culture where novel ideas are encouraged – even the smallest of ideas can spark the biggest breakthroughs. But these projects need support to get started – donations to the Cancer Immunology Fund allow our scientists to push the boundaries of cancer research. We are incredibly grateful for all the support we receive and look forward to sharing the progress of these projects over the next few years.”