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.
Skip Nav Destination
Article navigation
16 April 2007
Article|
March 26 2007
Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy
Radek Spisek,
Radek Spisek
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Search for other works by this author on:
Anjli Kukreja,
Anjli Kukreja
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Search for other works by this author on:
Lin-Chi Chen,
Lin-Chi Chen
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Search for other works by this author on:
Phillip Matthews,
Phillip Matthews
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Search for other works by this author on:
Amitabha Mazumder,
Amitabha Mazumder
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
Search for other works by this author on:
David Vesole,
David Vesole
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
Search for other works by this author on:
Sundar Jagannath,
Sundar Jagannath
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
Search for other works by this author on:
Henry A. Zebroski,
Henry A. Zebroski
9Proteomics Resource Center, The Rockefeller University, New York, NY 10021
Search for other works by this author on:
Andrew J.G. Simpson,
Andrew J.G. Simpson
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Search for other works by this author on:
Gerd Ritter,
Gerd Ritter
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Search for other works by this author on:
Brian Durie,
Brian Durie
6Cedars-Sinai Medical Center, Los Angeles, CA 90048
Search for other works by this author on:
John Crowley,
John Crowley
5Southwest Oncology Group Statistical Center, Seattle, WA 98109
Search for other works by this author on:
John D. Shaughnessy, Jr.,
John D. Shaughnessy, Jr.
7Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Search for other works by this author on:
Matthew J. Scanlan,
Matthew J. Scanlan
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Search for other works by this author on:
Ali O. Gure,
Ali O. Gure
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
8Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey
Search for other works by this author on:
Bart Barlogie,
Bart Barlogie
7Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Search for other works by this author on:
Madhav V. Dhodapkar
Madhav V. Dhodapkar
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Search for other works by this author on:
Radek Spisek
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Anjli Kukreja
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Lin-Chi Chen
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Phillip Matthews
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
Amitabha Mazumder
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
David Vesole
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
Sundar Jagannath
4St. Vincent's Comprehensive Cancer Center, New York, NY 10011
Henry A. Zebroski
9Proteomics Resource Center, The Rockefeller University, New York, NY 10021
Andrew J.G. Simpson
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Gerd Ritter
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Brian Durie
6Cedars-Sinai Medical Center, Los Angeles, CA 90048
John Crowley
5Southwest Oncology Group Statistical Center, Seattle, WA 98109
John D. Shaughnessy, Jr.
7Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Matthew J. Scanlan
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
Ali O. Gure
3New York Branch of Human Cancer Immunology, Ludwig Institute for Cancer Research, New York, NY 10021
8Department of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, Turkey
Bart Barlogie
7Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Madhav V. Dhodapkar
1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021
CORRESPONDENCE Madhav V. Dhodapkar: [email protected]
Abbreviations used: AMM, asymptomatic MM; BMMNC, bone marrow MNC; EBNA, Epstein-Barr nuclear antigen; IP-10, IFN-γ–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.
Dr. Scanlan died on 12 March 2004.
Received:
November 14 2006
Accepted:
February 28 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (4): 831–840.
Article history
Received:
November 14 2006
Accepted:
February 28 2007
Connected Content
Citation
Radek Spisek, 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, John D. Shaughnessy, Matthew J. Scanlan, Ali O. Gure, Bart Barlogie, Madhav V. Dhodapkar; Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy . J Exp Med 16 April 2007; 204 (4): 831–840. doi: https://doi.org/10.1084/jem.20062387
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
