Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy.
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.
Spisek
Radek
R
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
Kukreja
Anjli
A
Chen
Lin-Chi
LC
Matthews
Phillip
P
Mazumder
Amitabha
A
Vesole
David
D
Jagannath
Sundar
S
Zebroski
Henry A
HA
Simpson
Andrew J G
AJ
Ritter
Gerd
G
Durie
Brian
B
Crowley
John
J
Shaughnessy
John D
JD
Scanlan
Matthew J
MJ
Gure
Ali O
AO
Barlogie
Bart
B
Dhodapkar
Madhav V
MV
D015415:Biomarkers; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000276:immunology*; D024002:HMGB Proteins / Q000276:immunology* / Q000378:metabolism; D006262:Health; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010265:Paraproteinemias / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D055748:SOXB1 Transcription Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
D015415:Biomarkers; D024002:HMGB Proteins; D007074:Immunoglobulin G; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors