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

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Spisek R., Kukreja A., Chen L., Matthews P., Mazumder A., Vesole D., ...More

JOURNAL OF EXPERIMENTAL MEDICINE, vol.204, no.4, pp.831-840, 2007 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 204 Issue: 4
  • Publication Date: 2007
  • Doi Number: 10.1084/jem.20062387
  • Page Numbers: pp.831-840


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.