ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B. Krasieva, Sebastien de Feraudy, Bruce J. Tromberg, Sharon Huang, Chad P. Garner, Jie Wu, Dave S. Hoon, Anand K. Ganesan
Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth.

Graphical abstract

Teaser

Tumors grow not only because they acquire mutations that promote their growth but also because they prevent the immune system from recognizing them. Chen et al. identify ATR mutations in human melanoma tumors and determine that ATR mutant melanomas harness the immune system to accelerate tumor growth.


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