Molecular profiling of melanoma tumours explains differences in survival after T cell therapy

November 28, 2017, Lund University

The more times metastasised melanoma has mutated and the patient's immune system has been activated against the tumour – the better the chances of survival after immunotherapy. This is what emerges from a research collaboration between Lund University in Sweden and Herlev university hospital in Denmark. The findings are now published in the scientific journal Nature Communications.

Using the body's own immune system to combat tumours, an approach known as immunotherapy, has brought a major breakthrough in cancer care. Whereas we previously had no treatments able to increase survival for certain cancer diagnoses, it is now possible to treat advanced melanoma, for example.

One such immunotherapy method currently under clinical trial on with advanced melanoma is adoptive T cell therapy. The treatment is demanding both in terms of resources and for the patient, who needs to be in a condition to withstand it.

Sharpens the T cells

In simple terms, the treatment entails first removing the patient's own T from the . T cells are the part of the immune system that recognises . The patient's cells are then cultured in the lab and subsequently injected back into the patient.

"The aim is for them to seek out and fight the tumour and the circulating tumour cells," explains Göran Jönsson, researcher at Lund University. He is collaborating with Herlev university hospital in Copenhagen, which is one of few hospitals in Europe currently conducting clinical trials of this form of immunotherapy.

Although the treatment outcomes are promising, only just below half of patients respond to this immunotherapy.

"Between 10 and 20 per cent of those affected by advanced melanoma can be cured with a single treatment of adoptive T cell therapy. On the other hand, the treatment is very intensive, and has many side effects. It is therefore important to be able to predict which patients stand to benefit from the treatment, so that we give it to the right ones," say Inge Marie Svane and Marco Donia, physicians at Herlev university hospital and researchers at the University of Copenhagen.

The more mutations, the better

In order to find such markers, the researchers studied a group of 25 patients who had all undergone adoptive T cell therapy for advanced melanoma, because they either did not respond to previous treatment or had a recurrence of disease during previous treatment. The researchers analysed tumour cells from the patients at the molecular level.

This revealed that the more mutations the tumour had, the better the result of the T cell therapy.

"We could show that the more mutations there were, the better. This is linked to the fact that every time the tumour mutates, new antigens are produced, known as neoantigens, that the T cells recognise as alien and want to fight. More mutations means more neoantigens for the immune system to discover," says Göran Jönsson.

It's like a game of hide and seek: the more people join, the easier it is for the person searching to find those who are hiding.

The researchers also saw that the survival rate was better if the part of the patient's immune system that infiltrates the tumour was active, even if the had not defeated the tumour.

"Because this treatment is not practised in many places in the world, the group of patients we can study is not very large, but our results clearly show a group of patients that can be identified on the who will have long-term benefits from the ," says Göran Jönsson.

Explore further: Cancer cells play hide-and-seek with immune system

More information: Martin Lauss et al. Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma, Nature Communications (2017). DOI: 10.1038/s41467-017-01460-0

Related Stories

Cancer cells play hide-and-seek with immune system

June 29, 2016
When the immune system attacks cancer, the tumour modifies itself to escape the immune reaction. Researchers at LUMC published on this subject in Nature on 28 June.

Localised immunotherapy new possibility to treat bladder cancer

December 8, 2016
Antibody-based immunotherapy is a new promising method to treat cancer. Unfortunately, today's treatments can result in adverse side effects. New findings from IGP show an alternative way to administer the therapy, which ...

Cancer can be combated with reprogrammed macrophage cells

May 20, 2016
Researchers at Karolinska Institutet have generated antibodies that reprogramme a type of macrophage cell in the tumour, making the immune system better able to recognise and kill tumour cells. The study, which is published ...

How "sleeper cells" in cancerous tumours can be destroyed

October 26, 2017
In many metastasised types of cancer, disseminated tumours grow back despite successful chemotherapy. As a research team under the direction of the University of Bern, Switzerland, has now discovered, this is because of isolated ...

Researchers discover new immunotherapy combination effective at killing cancer cells

August 29, 2017
Immunotherapy is an emerging field in the global fight against cancer, even though scientists and clinicians have been working for decades to find ways to help the body's immune system detect and attack cancerous cells. Doug ...

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Recommended for you

Fusion hybrids: A newly discovered population of tumor cells

September 24, 2018
In a recent study published in Science Advances, Charles E. Gast and co-workers detail the spontaneous process of cancer cell fusion with white blood cells to produce heterogenous hybrid clones in multiple biological systems, ...

Cancer cells evade immunotherapy by hiding telltale marker, suggesting how to stop relapse

September 24, 2018
Harnessing the immune system to treat cancer shows great promise in some patients, but for many, the response does not last long-term. In an effort to find out why, Fred Hutchinson Cancer Research Center scientists are using ...

In zebrafish, a way to find new cancer therapies, targeting tumor modulators

September 21, 2018
The lab of Leonard Zon, MD, at Boston Children's Hospital has long been interested in making blood stem cells in quantity for therapeutic purposes. Looking for a way to test for their presence in zebrafish, their go-to research ...

What can salad dressing tell us about cancer? Think oil and vinegar

September 20, 2018
Researchers led by St. Jude Children's Research Hospital scientists have identified another way the process that causes oil to form droplets in water may contribute to solid tumors, such as prostate and breast cancer. The ...

Novel biomarker found in ovarian cancer patients can predict response to therapy

September 20, 2018
Despite months of aggressive treatment involving surgery and chemotherapy, about 85 percent of women with high-grade wide-spread ovarian cancer will have a recurrence of their disease. This leads to further treatment, but ...

Testing fluorescent tracers used to help surgeons determine edges of breast cancer tumors

September 20, 2018
A team of researchers with members from institutions in The Netherlands and China has conducted a test of fluorescent tracers meant to aid surgeons performing tumor removal in breast cancer patients. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.