title: ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment.
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.
authors.affiliation: Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Chi-Fen
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Rolando
authors.initials: R
authors.lastname: Ruiz-Vega
authors.affiliation: Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Vasudeva
authors.affiliation: Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Espitia
authors.affiliation: Laser Microbeam and Medical Program, Beckman Laser Institute, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Krasieva
authors.affiliation: Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: de Feraudy
authors.affiliation: Laser Microbeam and Medical Program, Beckman Laser Institute, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Tromberg
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute (JWCI), Providence Saint John's Health Center, Santa Monica, CA 90404, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Chad P
authors.initials: CP
authors.lastname: Garner
authors.affiliation: Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute (JWCI), Providence Saint John's Health Center, Santa Monica, CA 90404, USA.
authors.forename: Dave S
authors.initials: DS
authors.lastname: Hoon
authors.affiliation: Department of Dermatology, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: aganesan@uci.edu.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Ganesan
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D002452:Cell Count; D049109:Cell Proliferation; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D000073658:Loss of Function Mutation; D008264:Macrophages / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009506:Nevus / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: C576897:Atr protein, mouse; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf
keywords: ATR; macrophage; melanoma; tumor microenvironment