title: A three-signal model of T-cell lymphoma pathogenesis.
abstract: T-cell lymphoma pathogenesis and classification have, until recently, remained enigmatic. Recently performed whole-exome sequencing and gene-expression profiling studies have significant implications for their classification and treatment. Recurrent genetic modifications in antigen ("signal 1"), costimulatory ("signal 2"), or cytokine receptors ("signal 3"), and the tyrosine kinases and other signaling proteins they activate, have emerged as important therapeutic targets in these lymphomas. Many of these genetic modifications do not function in a cell-autonomous manner, but require the provision of ligand(s) by constituents of the tumor microenvironment, further supporting the long-appreciated view that these lymphomas are dependent upon and driven by their microenvironment. Therefore, the seemingly disparate fields of genomics and immunology are converging. A unifying "3 signal model" for T-cell lymphoma pathogenesis that integrates these findings will be presented, and its therapeutic implications briefly reviewed.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Wilcox
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D019672:Genes, T-Cell Receptor; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D058990:Molecular Targeted Therapy; D053262:Receptors, OX40 / Q000235:genetics; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D018106:CD28 Antigens; D016207:Cytokines; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human