Why is Skin Cancer so Elusive?

When researchers begin thinking about how to eradicate cancer, they are increasingly considering the immune response and how it’s interplay results in control (in some cases) or the lack of control of the growth. By revealing these immune responses, research teams can identify strengths and weaknesses that can be manipulated, avoided or enhanced to produce a better outcome for the cancer patient and their overall health.

A team of researchers at the Mainz University Medical Center are working to reveal a new signal pathway used by skin cancer cells to evade attacks from the immune system altogether thereby increasing the odds that cancer can survive and thrive.

Skin cancer is defined as the abnormal growth of skin cells most often developing on skin exposed to the sun. Some common forms of skin cancer can also occur in areas of the skin not ordinarily exposed to sunlight. The most common three types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and melanoma. "In our paper in Nature Immunology, we report on a previously unknown immunoevasion mechanism used by the type of skin cancer known as melanoma," said Dr. Toszka Bohn, a researcher at the Institute for Immunology of the Mainz University Medical Center.

Melanoma can develop anywhere on the body, in otherwise normal skin or in an existing mole that becomes cancerous. Melanoma can affect people of any skin tone. The signs and symptoms of melanoma include a large brownish spot with darker speckles, a mole that changes in color, size or feel, a small lesion with an irregular border and portions that appear red, white, blue or blue-black.

The research team can display an increase in metabolic turnover in melanoma — this high turnover of energy results in abnormal acidification of the tumor environment. Due to the rise in an acidic environment, macrophages – the immune cells employed in anti-inflammation – develop into M2 macrophages, a sub-type of the anti-inflammatory molecule involved in the regeneration of tissue damage. This new development, interestingly, now assists in the survival of the cancer cells.

The team identifies a protein known as inducible cAMP early repressor (ICER). ICER is a protein that allows to the normal macrophages to develop into the MD sub-type macrophages.

By way of an animal model and through human tissue samples the team can prove their findings. "In an animal model we were further able to prove that the immune response to tumors is boosted or, in other words, the growth of cancer is slowed, if we eliminate ICER or interrupt the corresponding signal pathway," explains one of the scientists. "Comparable results obtained in analogous experiments using human tissue as samples underline the clinical relevance of our findings."

The team of researchers has successfully aided in the overall knowledge of how melanoma can effectively evade elimination by making use of the immune mechanisms that promote their survival in this example. The team hopes this knowledge will be used in future studies to combat cancer.

Sources: Nature Immunology, Science Daily, Mayo Clinic, YouTube