How skin cancer cells sidestep the immune system

November 29, 2018, Universitaet Mainz

Researchers at the Mainz University Medical Center have discovered a new signal pathway employed by skin cancer cells to avoid attack by the immune system. In an animal model and through analysis of human tissue samples, Dr. Toszka Bohn, Dr. Steffen Rapp and Professor Tobias Bopp were able to demonstrate the significant role played by a specific protein called ICER. Tumors grow less rapidly when ICER is not present. The researchers recently presented their study in Nature Immunology.

Over the course of evolution, the immune system has developed effective mechanisms to detect pathogens invading the body from outside and to eliminate them before they can cause major damage. However, the body is also exposed to dangers from inside. Such threats can take the form of genetic mutations from which a can ultimately develop. But how do these elude detection by the immune system? Which immune evasion mechanisms do they use? In order to be able to develop new immunotherapy approaches in the , it is first necessary to identify these mechanisms.

"In our paper in Nature Immunology, we report on a previously unknown immunoevasion mechanism used by the type of skin known as melanoma," said Dr. Toszka Bohn, researcher at the Institute for Immunology of the Mainz University Medical Center.

Among other things, are characterized by very rapid growth. The cells of tumors need a great deal of energy for this, which they obtain by means of a high rate of metabolic turnover. "We were able to show that the rate of metabolic turnover in melanomas is particularly high, which results in an abnormal acidification of the tumor environment," explained Professor Tobias Bopp, co-author and spokesperson of the Research Center for Immunotherapy (FZI). Because of this acidic micromilieu, certain immune cells called macrophages that have migrated into the tumor develop into M2 macrophages, which are a specific sub-type of anti-inflammatory macrophage.

M2 macrophages are usually involved in wound healing processes and the regeneration of damaged tissue. These properties now benefit the growth of the tumor. Through a more detailed analysis of the mechanism, the researchers discovered that a protein known as inducible cAMP early repressor (ICER) is substantially involved in the process of macrophage transformation into the M2 sub-type.

"In an we were further able to prove that the to tumors is boosted or, in other words, the growth of cancer is slowed, if we eliminate ICER or interrupt the corresponding signal pathway," Dr. Toszka Bohn pointed out. "Comparable results obtained in analogous experiments using human tissue as samples underline the clinical relevance of our findings."

The ICER protein, which the team in Mainz is investigating, is the focus of one of 18 sub-projects of the new Collaborative Research Center (CRC) 1292 on "Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections" that was set up in January 2018. "The mechanism identified through our work provides new insight into how the can be hampered when it comes to fighting cancer, thus giving us potential options for developing innovative treatment approaches," concluded Professor Hansjörg Schild, spokesperson of CRC 1292. The goal of the CRC is to build on the knowledge gained to develop new personalized immunotherapies for the treatment of both cancers and chronic infections.

Explore further: Cancer under pressure: Visualizing the activity of the immune system on tumor development

More information: Toszka Bohn et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages, Nature Immunology (2018). DOI: 10.1038/s41590-018-0226-8

Related Stories

Cancer under pressure: Visualizing the activity of the immune system on tumor development

November 28, 2018
As tumors develop, they evolve genetically. How does the immune system act when faced with tumor cells? How does it exert pressure on the genetic diversity of cancer cells? Scientists from the Institut Pasteur and Inserm ...

New immunotherapy inhibits tumor growth and protects against metastases

August 27, 2018
Scientists at the VIB-UGent Center for Medical Biotechnology have taken important steps toward the development of cancer-targeting immunotherapy. The research team developed a treatment in mice that destroys part of the tumor ...

Drug combination overcomes barrier to effective melanoma immunotherapy

April 12, 2018
Immunotherapies are treatments that stimulate a patient's immune cells to attack tumors. They can be very effective in melanoma—a common and aggressive form of skin tumor—but nonetheless fail in the majority of patients. ...

A cascade of immune processes offers insights to triple-negative breast cancer

May 24, 2018
Cancer is crafty. To survive and thrive, tumors find a way of thwarting our body's natural systems.

New cancer immunotherapy shows promise in early tests

July 2, 2018
Much cancer immunotherapy research has focused on harnessing the immune system's T cells to fight tumors, "but we knew that other types of immune cells could be important in fighting cancer too," says Ashish Kulkarni at the ...

Researchers discover new approach to stimulate an immune response against tumor cells

January 30, 2018
New drugs that activate the immune system to target cancer cells have improved the lives of many patients with cancer. However, immunotherapies are not effective in all patients, and the success of these therapies depends ...

Recommended for you

HIV vaccine protects non-human primates from infection

December 14, 2018
For more than 20 years, scientists at Scripps Research have chipped away at the challenges of designing an HIV vaccine. Now new research, published in Immunity, shows that their experimental vaccine strategy works in non-human ...

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

The 'greying' of T cells: Scientists pinpoint metabolic pathway behind age-related immunity loss

December 13, 2018
The elderly suffer more serious complications from infections and benefit less from vaccination than the general population. Scientists have long known that a weakened immune system is to blame but the exact mechanisms behind ...

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Surgery unnecessary for many prostate cancer patients

December 13, 2018
Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian ...

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.