Nav: Home

Tumors contain the seeds of their own destruction

March 03, 2016

SCIENTISTS have made a groundbreaking discovery in understanding how the genetic complexity of tumours can be recognised and exploited by the immune system, even when the disease is at its most advanced stages.

The findings, by researchers funded by Cancer Research UK and the Rosetrees Trust, could guide future immunotherapies and improve the way existing immunotherapy drugs are used.

As a tumour develops, the diversity of its genetic faults can be flagged on the cancer cell surface, as unique mutations appear in different parts of the tumour.

Crucially, by analysing data from hundreds of patients from previous studies, researchers found that some of these flags - known as antigens - represent the very earliest mutations of the disease and are displayed on all cells in the tumour, rather than a subset of tumour cells.

Then in the lab, they isolated specialised immune cells, called T-cells, from samples of two patients with lung cancer that can recognise these common flags present on every tumour cell.

Although they have the potential to wipe out all cancerous cells within the tumour, these potent immune cells are switched off by the tumour's defences.

This research paves the way for therapies that specifically activate these T cells to target all the tumour cells at once based on the disease's genetic signature. In the future, scientists could exploit this by developing a therapeutic vaccine to activate T-cells, or harvesting, growing and administering T-cells back into the patient that recognise the antigens common to every cancer cell.

Dr Sergio Quezada, co-author of the study, Cancer Research UK scientist and head of the Immune Regulation and Cancer Immunotherapy lab at UCL Cancer Institute, said: "The body's immune system acts as the police trying to tackle cancer, the criminals. Genetically diverse tumours are like a gang of hoodlums involved in different crimes - from robbery to smuggling. And the immune system struggles to keep on top of the cancer - just as it's difficult for police when there's so much going on.

"Our research shows that instead of aimlessly chasing crimes in different neighbourhoods, we can give the police the information they need to get to the kingpin at the root of all organised crime - or the weak spot in a patient's tumour - to wipe out the problem for good."

The genetic complexity of cancer**, which is flagged by tumour antigens, arises when cancers evolve in a branched manner. The earliest faults are found in all cells, forming the 'trunk' of the disease, while later mutations arise in some cells but not all. It is these 'branches' that allow the disease to adapt and become drug resistant.

Professor Charles Swanton, co-author from the UCL Cancer Institute and a Francis Crick Institute scientist, said: "This is exciting. There was evidence that complex tumours with many mutations could increase the chance of the immune system spotting them; now we can prioritise and target tumour antigens that are present in every cell, the Achilles heel of these highly complex cancers.

"This opens up a way to look at individual patients' tumours and profile all the antigen variations to figure out the best ways for immunotherapy treatments to work, prioritising antigens present in every tumour cell and identifying the body's immune T cells that recognise them. This is really fascinating, and takes personalised medicine to its absolute limit where each patient would have a unique, bespoke treatment."

Dr Quezada added: "For many years we have studied how the immune response to cancer is regulated without a clear understanding of what it is that immune cells recognise on cancerous cells. Based on these new findings, we will be able to tell the immune system how to specifically recognise and attack tumours."

Professor Peter Johnson, Cancer Research UK's chief clinician, said: "This fascinating research gives us vital clues about how to specifically tailor treatment for a patient using their immune system.

"It gets us closer to knowing why some patients respond to immunotherapy treatment and others don't, and how we might select which patients will benefit the most.

"As well as suggesting a new way to treat cancer, the research fills key gaps in our knowledge about the effects of the immune system on tumours. This gives us hope of developing better treatments for some of the cancers we have previously found hardest to treat."

Sam Howard, Chief Executive of Rosetrees Trust, said: "Rosetrees Trust is delighted to be able to support such cutting edge research carried out by outstanding researchers, which potentially has a direct human impact."

This research is published today (Thursday) in Science.
-end-
For media enquiries contact Stephanie McClellan in the Cancer Research UK press office on 020 3469 5314 or, out of hours, on 07050 264 059.

Notes to editor:


* McGranahan et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science

** This phenomenon was first reported by Cancer Research UK scientists in 2012 who were studying kidney cancer. This followed work at The Institute of Cancer Research that had found the same in blood cancers.

Link to animation: https://www.dropbox.com/s/0nbx5amtaban8x4/CRUK_Heterogeneity_final_edit_SOUND_total.mp4?dl=0

About Cancer Research UK
  • Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
  • Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
  • Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated.
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that 3 in 4 people will survive their cancer for at least 10 years within the next 20 years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit http://www.cancerresearchuk.org. Follow us on Twitter and Facebook.

About Rosetrees Trust

Rosetrees Trust is a substantial family foundation established in 1987 that funds life changing medical research. Rosetrees enables outstanding medical researchers, often at the start of their career, to conduct early stage research. Under the guidance of top researchers, it gives them the opportunity to experiment with ideas and become future leaders in their field. Rosetrees believes that basic (rather than just translational) research is a crucial cog in the scientific wheel and can, ultimately, lead to the major discoveries of our generation. The UK has world class medical research, but lacks funding - especially seed corn funding. Rosetrees aims to change that.

Rosetrees currently supports over 250 live medical research projects, and since establishment over 25 years ago, in excess of £240 million has been invested in world class research, either from Rosetrees, co donations or the major grants that followed from Rosetrees' initial support. Rosetrees has a target of generating £1 billion for medical research.

Rosetrees' unique entrepreneurial philanthropy model sources and selects only the best projects and researchers to support, and then carefully manages the funding throughout the duration. Rosetrees actively seeks trusts and philanthropists to co donate with in order to direct more funds to the best medical research projects, and co donors who fund alongside Rosetrees benefit at no cost from this expertise. http://www.rosetreestrust.co.uk Follow us @RosetreesT

Cancer Research UK

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.