title: Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy.
abstract: Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of spontaneous immunity in MGUS differ from MM. MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells. Intranuclear expression of SOX2 marks the clonogenic CD138(-) compartment in MGUS. SOX2 expression is also detected in a proportion of CD138(+) cells in MM patients. However, these patients lack anti-SOX2 immunity. Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro. Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders. Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer.
authors: Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
authors: Radek
authors: R
authors: Spisek
authors: Anjli
authors: A
authors: Kukreja
authors: Lin-Chi
authors: LC
authors: Chen
authors: Phillip
authors: P
authors: Matthews
authors: Amitabha
authors: A
authors: Mazumder
authors: David
authors: D
authors: Vesole
authors: Sundar
authors: S
authors: Jagannath
authors: Henry A
authors: HA
authors: Zebroski
authors: Andrew J G
authors: AJ
authors: Simpson
authors: Gerd
authors: G
authors: Ritter
authors: Brian
authors: B
authors: Durie
authors: John
authors: J
authors: Crowley
authors: John D
authors: JD
authors: Shaughnessy
authors: Matthew J
authors: MJ
authors: Scanlan
authors: Ali O
authors: AO
authors: Gure
authors: Bart
authors: B
authors: Barlogie
authors: Madhav V
authors: MV
authors: Dhodapkar
mesh_terms: D015415:Biomarkers; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000276:immunology*; D024002:HMGB Proteins / Q000276:immunology* / Q000378:metabolism; D006262:Health; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010265:Paraproteinemias / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D055748:SOXB1 Transcription Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024002:HMGB Proteins; D007074:Immunoglobulin G; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors