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

  • Author(s): Chen, Chi-Fen
  • Ruiz-Vega, Rolando
  • Vasudeva, Priya
  • Espitia, Francisco
  • Krasieva, Tatiana B
  • de Feraudy, Sebastien
  • Tromberg, Bruce J
  • Huang, Sharon
  • Garner, Chad P
  • Wu, Jie
  • Hoon, Dave S
  • Ganesan, Anand K
  • et al.
Creative Commons Attribution 4.0 International Public License
Abstract

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.

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