NDLI: Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab

Content Provider	PubMed Central
Author	Yuan, Jianda Matthew, Adamow Ginsberg, Brian A. Rasalan, Teresa S. Ritter, Erika Gallardo, Humilidad F. Xu, Yinyan Pogoriler, Evelina Terzulli, Stephanie L. Kuk, Deborah Panageas, Katherine S. Ritter, Gerd Mario, Sznol Halaban, Ruth Jungbluth, Achim A. Allison, James P. Old, Lloyd J. Wolchok, Jedd D. Gnjatic, Sacha
Abstract	Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1–seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1–seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1–specific CD4+ and CD8+ T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1–seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1–seropositive patients with associated CD8+ T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8+ T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.
Related Links	http://dx.doi.org/10.1073/pnas.1110814108
Ending Page	16728
Page Count	6
Starting Page	16723
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	40
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-10-04
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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