Browsing by Subject "HMGB Proteins"
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Item Open Access Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy(Rockefeller University Press, 2007) Spisek, R.; Kukreja, A.; Chen, L. -C.; Matthews, P.; Mazumder, A.; Vesole, D.; Jagannath, S.; Zebroski, H. A.; Simpson, A. J. G.; Ritter, G.; Durie, B.; Crowley, J.; Shaughnessy, Jr. J.D.; Scanlan, M. J.; Gure, A. O.; Barlogie, B.; Dhodapkar, M. V.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.