title: Leveraging premalignant biology for immune-based cancer prevention.
abstract: Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system's ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118;
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195;
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vilar
authors.affiliation: Dana-Farber Cancer Institute, Harvard T. H. Chan School of Public Health, Boston, MA 02215;
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.affiliation: Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093;
authors.forename: Rafael
authors.initials: R
authors.lastname: Bejar
authors.affiliation: Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093;
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
authors.affiliation: Janssen Oncology Research & Development, Pharmaceutical Companies of Johnson & Johnson, 2300 Beerse, Belgium;
authors.forename: Janine
authors.initials: J
authors.lastname: Arts
authors.affiliation: Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215;
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Yurgelun
authors.affiliation: Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093;
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
authors.affiliation: Department of Medical Oncology, Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA 02215;
authors.forename: Judy
authors.initials: J
authors.lastname: Garber
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.affiliation: Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093; slippman@ucsd.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000473:pathology; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D009363:Neoplasm Proteins
keywords: biology; cancer prevention; immune oncology; premalignancy; vaccines