ATR mutations increase skin cancer tumor growth by modulating the tumor microenvironment.
Investigators identified a mechanism used by melanoma cells to modulate the immune microenvironment to promote continued growth, according to a study.
The findings, published in Cell Reports, may lead to the development of improved immunotherapies. Furthermore, it could help develop methods to determine which patients would respond to treatment.
“Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth,” the authors wrote.
The investigators sought to examine whether ATR mutations contributed to the development of melanoma.
During the study, investigators identified a mutation in the ATR gene—–a protein that recognizes and repairs UV-induced DNA damage––in melanoma tumors. The findings showed that cancers with ATR mutations suppress the body’s natural immune response.
“Cancers develop not only because they acquire mutations that promote their growth but also because they are able to prevent the immune system from recognizing and removing them,” said senior author Anand K. Ganesan, MD. “Understanding how developing tumors interact with the immune system to promote their continued growth is a key to developing effective immunotherapies.”
Although melanoma only accounts for approximately 1% of all skin cancers, it causes a large majority of skin cancer deaths. The American Cancer Society estimates approximately 87,110 new cases of melanoma will be diagnosed in the United States in 2017, of which, approximately 9730 individuals are expected to die of the disease.
Melanoma is more than 20 times more common in whites than in African Americans. The average age of diagnosis is 63 years, and the risk of developing the disease increases with age.