Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy

• Type of Material: Article
• Authors: Radek Spisek, Rockefeller University; Anjil Kukreja, Rockefeller University; Lin-Chi Chen, Memorial Sloan-Kettering Cancer Center; Phillip Matthews, Rockefeller University; Amitabha Mazumder, St. Vincent's Comprehensive Cancer Center; David Vesole, St. Vincent's Comprehensive Cancer Center; Sundar Jagannath, St. Vincent's Comprehensive Cancer Center; Henry A. Zebroski, Rockefeller University; Andrew J. G. Simpson, Ludwig Institute for Cancer Research; Gerd Ritter, Ludwig Institute for Cancer Research; Brian Durie, Cedars-Sinai Medical Center; John Crowley, Southwest Oncology Group Statistical Center; John D. Shaughnessy Jr., University of Arkansas; Matthew J. Scanlan, Ludwig Institute for Cancer Research; Ali O. Gure, Ludwig Institute for Cancer Research; Bart Barlogie, University of Arkansas; Madhav Dhodapkar, Emory University
• Language: English
• Date: 2007-04-16
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: JEM © The Rockefeller University Press.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.20062387
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 204
• Issue: 4
• Start Page: 831
• End Page: 840
• Grant/Funding Information: This work was supported in part by funds from the National Institutes of Health (grants CA106802, CA109465, P50-AT02779, MO1-RR00102, and PO1-CA55819), an Eli Lilly-Damon Runyon Clinical Investigator Award, the Dana Foundation, the Irma T. Hirschl Foundation, the Fund to Cure Myeloma, and the Southwest Oncology Group.
• Keywords: IMMUNOGENIC TUMOR-ANTIGENS; DENDRITIC CELLS; CANCER; Research & Experimental Medicine; MULTIPLE-MYELOMA; IMMUNOPREVENTION; Medicine, Research & Experimental; Science & Technology; ANTIBODIES; T-CELLS; Immunology; RESPONSES; TARGETS; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

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.