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¹ Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
² Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
³ New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
⁴ St. Vincent's Comprehensive Cancer Center, New York, NY 10011
⁵ Southwest Oncology Group Statistical Center, Seattle, WA 98109
⁶ Cedars-Sinai Medical Center, Los Angeles, CA 90048
⁷ Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205
⁸ Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey
⁹ Proteomics Resource Center, The Rockefeller University, New York, NY 10021

CORRESPONDENCE Madhav V. Dhodapkar: dhodapm{at}rockefeller.edu

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.

Abbreviations used: AMM, asymptomatic MM; BMMNC, bone marrow MNC; EBNA, Epstein-Barr nuclear antigen; IP-10, IFN-–inducible protein 10; MGUS, monoclonal gammopathy of undetermined significance; MM, myeloma; MNC, mononuclear cell; SADA, serum antibody detection array; SEREX, serological expression of cDNA expression libraries.

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