title: Genomic alterations underlying immune privilege in malignant lymphomas.
abstract: OBJECTIVE
  Malignant lymphomas represent a remarkably heterogeneous group of cancers with respect to their oncogenome, phenotype and clinical presentation. Lymphoma cells benefit from limited immune surveillance and have developed various mechanisms to alter antitumor immune responses. This article summarizes our current knowledge about genomic alterations underlying acquired immune privilege in lymphoid cancers.
  
  
  RESULTS
  The implementation and broad application of next-generation sequencing techniques have significantly expanded our knowledge about genetic alterations and perturbed cellular pathways underlying lymphomagenesis. Based on key discoveries in the past decade, the purview of subsequent studies expanded beyond the biology of the lymphoma cells to include the pathogenic contribution of immune cells, stromal components and associated crosstalk between malignant and nonmalignant cells in the tumor microenvironment. A number of genetic mechanisms have been described that elucidate how lymphoma cells are selected for evading immune recognition and reprogramming immune responses. These prominently include structural genomic changes of the CIITA and programmed death ligand (CD274/PDCD1LG2) loci, alterations affecting antigen presentation and mutations in JAK-STAT and NFκB signaling pathways.
  
  
  CONCLUSIONS
  Further investigations will foster our understanding about synergy of immune escape mechanisms, and lay the foundation for the development of predictive biomarkers in the context of conceptually novel therapies targeting microenvironment-related biology, such as immunological checkpoint inhibition.
authors.affiliation: aCentre for Lymphoid Cancer, BC Cancer Agency bDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Anja
authors.initials: A
authors.lastname: Mottok
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics* / Q000276:immunology; D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D007157:Immunologic Surveillance; D053612:Janus Kinases / Q000235:genetics / Q000276:immunology; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology; D019139:Tumor Escape / Q000235:genetics*; D059016:Tumor Microenvironment
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C083728:MHC class II transactivator protein; D016328:NF-kappa B; D009687:Nuclear Proteins; D050791:STAT Transcription Factors; D015534:Trans-Activators; D053612:Janus Kinases