Nav: Home

Origins of immune system mapped, opening doors for new cancer immunotherapies

February 20, 2020

A first cell atlas of the human thymus gland could lead to new immune therapies to treat cancer and autoimmune diseases. Researchers from the Wellcome Sanger Institute, Newcastle University and Ghent University, Belgium, mapped thymus tissue through the human lifespan to understand how it develops and makes vital immune cells called T cells. In the future, this information could help researchers to generate an artificial thymus and engineer improved therapeutic T cells.

Published today (20 February) in Science, this human thymus atlas has revealed new cell types and identified signals that tell immature immune cells how to develop into T cells. The atlas could also help scientists understand diseases that affect T cell development such as severe combined immunodeficiency (SCID), and adds to the Human Cell Atlas initiative which is creating a Google map of the entire human body.

The thymus gland is located in the chest and produces T cells, key white blood cells that fight infection and disease. These T cells then leave the thymus to enter the blood and other parts of the body to mature further. T cells seek out and destroy invading bacteria and viruses, and also recognise cancer cells and kill them.

Problems in thymus development causes defective T cell generation. This can result in severe immune deficiencies such as SCID, leaving people susceptible to infections. Alternatively, it can affect T cell regulation resulting in autoimmune diseases such as Type 1 diabetes. While mature T cells have been well studied, the development of the human thymus and T cells within it is not fully understood.

Researchers used single cell technology to isolate and analyse around 200,000 individual cells from the developing thymus, and child and adult thymus tissue. They looked at which genes were active in each individual cell to identify the cells, discovering new cell types, and used those genes as tags to map each cell to its exact location in the thymus.

Dr Jongeun Park, the first author on the study from the Wellcome Sanger Institute, said: "We have produced a first human thymus cell atlas to understand what is happening in the healthy thymus across our lifespan, from development to adulthood, and how it provides the ideal environment to support the formation of T cells. This openly available resource will allow researchers worldwide to understand how the immune system develops to protect our body."

Therapeutic T cells are currently being used in the clinic to treat B-cell lymphoma and leukaemia cancers*, however a major drawback to these treatments is creating the right subtype of T cells.

Professor Muzlifah Haniffa, a senior author of the study from Newcastle University and Senior Clinical Fellow at the Wellcome Sanger Institute, said: "With this thymus cell atlas, we are unravelling the cellular signals of the developing thymus, and revealing which genes need to be switched on to convert early immune precursor cells into specific T cells. This is really exciting as in the future, this atlas could be used as a reference map to engineer T cells outside the body with exactly the right properties to attack and kill a specific cancer - creating tailored treatments for tumours."

Professor Tom Taghon, a senior author of the study from Ghent University, Belgium, said: "We now have a very detailed understanding of how T cells form in healthy tissue. We have been able to identify a similar population of precursor cells in the developing thymus and liver, and we believe that these precursors are important for initiating T cell development in the foetus, and for the establishment of a fully competent thymus organ. This is helping us put jigsaw pieces together to get a bigger picture of how immunity develops."

The thymus is unusual in that it is largest and most active in childhood and shrinks after puberty. The thymus has been called the 'pacemaker of life' and by age 35 has almost disappeared. Understanding how the thymus develops and then withers could cast light on aging and how the immune system changes through life.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: "This map of the thymus is an important part of the Human Cell Atlas mission to chart every cell type in the human body. It is helping us learn about developmental pathways within the body, and the age-associated decline of the immune system. This has applications in cellular engineering, including the possibility of creating an artificial thymus for regenerative medicine."
-end-
Notes to Editors:

* CAR-T - chimeric antigen receptor T-cell - therapy is specifically developed for each individual patient and involves reprogramming the patient's own immune system cells which are then used to target their cancer. Car-T therapy can help children and young people with B cell acute lymphoblastic leukaemia and adults with diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma . https://www.england.nhs.uk/cancer/cdf/car-t-therapy/

Selected websites:

Institute of Cellular Medicine, University of Newcastle

We carry out world-class research to advance understanding of disease and improve patient care. More than half of our academic staff are clinicians. We have close working relationships with a large cohort of patients and the Newcastle-upon-Tyne Hospitals NHS Foundation Trust. Find out more at https://www.ncl.ac.uk/icm/about/

About Newcastle University

Newcastle University, UK, is a thriving international community of some 27,750 students from over 130 countries worldwide.

As a member of the Russell Group of research intensive universities in the UK, Newcastle has a world-class reputation for research excellence in the fields of medicine, science and engineering, social sciences and the humanities.

Its academics are sharply focused on responding to the major challenges facing society today. Our research and teaching are world-leading in areas as diverse as health, culture, technology and the environment.

The Research Excellence Framework 2014 (REF) placed Newcastle University 16th in the UK for Research Power and the vast majority of our research (78%) was assessed to be world-leading or internationally excellent.

Newcastle University is committed to providing our students with excellent, research-led teaching delivered by dedicated and passionate teachers. This is reaffirmed by achieving the best possible outcome - a Gold Award - in the Teaching Excellence Framework (TEF). https://www.ncl.ac.uk/press/about/keyfacts/

Ghent University

Ghent University is one of the major universities in the Dutch-speaking region of Europe. It distinguishes itself as a socially committed and pluralistic university in a broad international perspective. 86 faculty departments, spread over 11 faculties, offer high-quality courses in every one of their scientific disciplines. With a view to cooperation in research and community service, numerous research groups, centres and institutes have been founded over the years. http://www.UGent.be/en [ugent.be]

The Wellcome Sanger Institute

The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast - we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at http://www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

About Wellcome

Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation. https://wellcome.ac.uk/

Wellcome Trust Sanger Institute

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.