Key mutation in melanoma suppresses immune system
UC Irvine Health discovery may lead to immunotherapy treatment
March 07, 2017
University of California, Irvine researchers have identified a specific mutation that allows melanoma tumor cells to remain undetected by the immune system. The finding may lead to the development of better immunotherapies and more effective methods to identify patients that would respond to these new therapies.
The study, “ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment,” is published March 7 in the journal Cell Reports.
“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 Anand K. Ganesan, MD, senior author and Associate Professor at the University of California, Irvine. He explained that researchers identified a mutation in the ATR gene, a protein that normally recognizes and repairs UV-induced DNA damage, in melanoma tumors. Cancers with this ATR mutation suppress the body’s natural immune response.
“Understanding how developing tumors interact with the immune system to promote their continued growth is a key to developing effective immunotherapies,” he said.
Skin cancer is the most common of all cancers, according to the American Cancer Society. In 2017, it’s expected that more than 87,000 new melanomas will be diagnosed (about 52,170 in men and 34,940 in women) and that about 9,730 people are expected to die of the disease.
Participants in the study include Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Sebastien de Feraudy, Anand K. Ganesan, Jie Wu, Chad P. Garner, Tatiana B. Krasieva and Bruce J. Tromberg from the University of California, Irvine and Sharon Huang and David S. Hoon from the John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica.
This research was supported by grants from the National Cancer Institute (1R01CA151513-01), the American Cancer Society (121540-RSG-11-128-01-CSM), the National Science Foundation (DGE-1321846), the Ford Foundation National Academies of Science, Engineering, and Medicine Dissertation Fellowship and the Stanley Behrens Fellowship. The multiphoton microscopy studies were supported by National Institute of Biomedical Imaging and Bioengineering award P41EB015890. The genomic sequencing was performed by the UC Irvine Genomics and High Throughput Facility, which is supported in part by National Cancer Institute award P30CA062203.
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