Skin cancer evades immune therapies

Researchers at the University of Bonn believe they have pinpointed why treatments for melanomas, a type of skin cancer, are only temporarily effective. In a paper soon to be published in Nature, Landsberg et al. detail mechanisms by which malignant melanocytes are able to avoid detection and destruction by  immune cells used in adoptive cell transfer (ACT) therapies, by altering cell surface components known as antigens.

Melanocytes are specialised pigment cells that determine skin colour though the production of a dark pigment called melanin. Melanomas, a cancer of melanocytes, are dangerous due to an ability to spread quickly to locations including the brain. ACT therapies use modified cells of the body’s own defense system to detect specific antigens so as to target only the cancerous cells. While this can successfully cause remission initially, the cancer commonly recurs and this new research suggests a connection to inflammation caused by the therapy.

A compound called Tumour Necrosis Factor-α is released by the body during inflammation, was seen in mouse and human melanomas as a signal for change in cancerous cells. The cells displayed characteristics not associated with the melanocyte cell type meaning defensive cells could not detect and destroy them. As soon as the compound was removed, the cells returned to their original appearance.

The authors suggest that when using this treatment approach in future, immune cells should be modified to identify multiple types of antigen not just those specific to melanocytes. This way the cells in hiding might also be detected reducing the likelihood of the cancer reappearing. They also suggest that alongside this approach, inflammation should be minimised at the site of the cancer so the tumour cells are not encouraged to camouflage themselves.