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Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy

Jianda Yuan, David B. Page, Geoffrey Y. Ku, Yanyun Li, Zhenyu Mu, Charlotte Ariyan, Humilidad F. Gallardo, Ruth-Ann Roman, Agnes I. Heine, Stephanie L. Terzulli, Erika Ritter, Sacha Gnjatic, Gerd Ritter, Achim A. Jungbluth, James P. Allison, Lloyd J. Old and Jedd D. Wolchok
Jianda Yuan
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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David B. Page
2Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Geoffrey Y. Ku
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Yanyun Li
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Zhenyu Mu
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Charlotte Ariyan
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Humilidad F. Gallardo
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Ruth-Ann Roman
2Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Agnes I. Heine
2Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Stephanie L. Terzulli
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
2Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Erika Ritter
3Ludwig Institute for Cancer Research, New York Branch, New York, NY 10065, USA
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Sacha Gnjatic
3Ludwig Institute for Cancer Research, New York Branch, New York, NY 10065, USA
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Gerd Ritter
3Ludwig Institute for Cancer Research, New York Branch, New York, NY 10065, USA
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Achim A. Jungbluth
3Ludwig Institute for Cancer Research, New York Branch, New York, NY 10065, USA
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James P. Allison
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
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Lloyd J. Old
3Ludwig Institute for Cancer Research, New York Branch, New York, NY 10065, USA
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Jedd D. Wolchok
1Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY 10065, USA
2Melanoma/Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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DOI:  Published January 2010
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    Figure 1

    Immunogram of patient IMF-16. WBC and ALC are graphed in ×103/mm3 units; NY-ESO-1 titers are graphed in log10 as an inverse titer.

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    Figure 2

    Radiographic images of target lesions of patient IMF-16. Representative computer tomography (CT) images of IMF-16 demonstrating complete response in right lung lesions, progressive disease in right external iliac lymph nodes, and essentially stable subcarinal lymph nodes.

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    Figure 3

    CD4+ CD25+ and CD4+ FOXP3+ Tregs in peripheral blood and progressive right inguinal lymph node in patient IMF-16. CD4+ cells from the tumor tissue and from PBMCs were analyzed by flow cytometry and immunohistological staining for CD25 and FOXP3 expression. (A) Representative dot plots. (B) Compiled data. (C) CD4 immunohistochemical staining (clone BC/1F6). (D) FOXP3 immunohistochemical staining (clone 236A/E7).

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    Figure 4

    NY-ESO-1 antigen-specific CD8+ IFN-γ+ and CD4+ IFN-γ+ responses. The IFN-γ gate was set based on a negative control (alone) sample and applied across other samples (+NY-ESO-1). (A) Representative dot plots. (B) Compiled data. (C) MHC class I immunohistochemical staining (clone A4). (D) HLA-DR immunohistochemical staining (clone YE2/36HLK).

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    Figure 5

    Cancer/testis antigen expression on a progressive lymph node with tumor. Immunohistochemical staining of a lymph node metastasis for several cancer/testis antigens. Extensive immunoreactivity was seen with monoclonal antibodies (A) MA454 (to MAGE-A1), (B) M3H67 (to several MAGE-A antigens), (C) CT10-5 (to CT10/MAGE-C2), (D) E978 (to NY-ESO-1), (E) CT7-33 (to CT7/MAGE-C1), and (F) #26 (to GAGE).

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Cancer Immunity Archive: 10 (1)
January 2010
Volume 10, Issue 1
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Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy
Jianda Yuan, David B. Page, Geoffrey Y. Ku, Yanyun Li, Zhenyu Mu, Charlotte Ariyan, Humilidad F. Gallardo, Ruth-Ann Roman, Agnes I. Heine, Stephanie L. Terzulli, Erika Ritter, Sacha Gnjatic, Gerd Ritter, Achim A. Jungbluth, James P. Allison, Lloyd J. Old and Jedd D. Wolchok
Cancer Immun January 1 2010 (10) (1) 1;

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Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy
Jianda Yuan, David B. Page, Geoffrey Y. Ku, Yanyun Li, Zhenyu Mu, Charlotte Ariyan, Humilidad F. Gallardo, Ruth-Ann Roman, Agnes I. Heine, Stephanie L. Terzulli, Erika Ritter, Sacha Gnjatic, Gerd Ritter, Achim A. Jungbluth, James P. Allison, Lloyd J. Old and Jedd D. Wolchok
Cancer Immun January 1 2010 (10) (1) 1;
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