April 16, 2007
Source: J Exp Med 2007;204: 831-40.
Authors: Radek Špíšek, Anjli Kukreja, Lin-Chi Chen, Phillip Matthews, Amitabha Mazumder, David Vesole, Sundar Jagannath, Henry A. Zebroski, Andrew J.G. Simpson, Gerd Ritter, Brian Durie, John Crowley et al.
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.