Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy-Reference-Cited by-同舟云学术

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

Published:2007-03-26 Issue:4 Volume:204 Page:831-840
ISSN:1540-9538
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Spisek Radek¹,Kukreja Anjli¹,Chen Lin-Chi²,Matthews Phillip¹,Mazumder Amitabha³,Vesole David³,Jagannath Sundar³,Zebroski Henry A.⁴,Simpson Andrew J.G.⁵,Ritter Gerd⁵,Durie Brian⁶,Crowley John⁷,Shaughnessy John D.⁸,Scanlan Matthew J.⁵,Gure Ali O.⁵⁹,Barlogie Bart⁸,Dhodapkar Madhav V.¹

Affiliation:

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. St. Vincent's Comprehensive Cancer Center, New York, NY 10011

4. Proteomics Resource Center, The Rockefeller University, New York, NY 10021

5. New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021

6. Cedars-Sinai Medical Center, Los Angeles, CA 90048

7. Southwest Oncology Group Statistical Center, Seattle, WA 98109

8. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205

9. Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

http://rupress.org/jem/article-pdf/204/4/831/1400394/jem_20062387.pdf

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