When Cancer Therapy Backfires

Melanoma immunotherapy can trigger melanoma cells to hide by shifting forms

(RxWiki News) Triggering a patient’s natural immune response to treat melanoma can work well. But it can also cause melanoma cells to disguise themselves as another kind of cell.

A recent study set out to understand exactly why and how melanoma tumors treated with immunotherapy go away and then come back again. Melanoma cells can go undetected for a while this way, evade destruction and then reappear.

The study’s findings suggest targeting two different types of blood cells may offer a remedy for this paradox.

"Talk to your oncologist about treatment options."

Thomas Tüting, MD, professor in the Department of Dermatology at the University of Bonn in Germany, oversaw a team of melanoma researchers.

Dr. Tüting said, “The immune system is like a double-edged sword. It can fight the tumor – but it can also protect it.”

T cells are white blood cells that help the body’s immune system fight off invaders. Treatments called immunotherapy use T cells to target spreading melanoma tumor cells, which is a form of skin cancer.

By convincing the body to use its own immune system to attack cancer cells, tumors often go into remission. But with melanoma, the most serious form of skin cancer, the tumors can come back.

Researchers at the University of Bonn set out to understand why this T cell therapy either works, doesn’t work or works and then reverses itself in melanoma patients.

They discovered tumors can re-develop due to the inflammation caused by the T cell therapy itself. The inflammation changes the structure of the melanoma cells so T cells can no longer identify them as a threat.

Researchers were able to see that the shift in appearance of melanoma cells caused them to go from looking like pigment cells to looking like connective tissue cells.

Pigment, connective tissue and nerve cells are generated from the same place. This could explain why inflammation can mask melanoma cells to look like other cells.

Specific defense cells go after specific tumor cells. If the cells shift in reaction to the inflammation, the defense cells can no longer go after them—they are blind to other types of cells.

Dr. Tüting said, “Our experimental model system will help us to develop optimally effective combination therapies as rapidly as possible.”

Authors recommended future therapies target both melanoma specific T cells and non-melanoma specific T cells by blocking inflammation response in the tumor “microenvironment.”

This study was published in October in Nature.

No funding information was given. No conflicts of interest were reported.

Review Date: 
October 29, 2012