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


Authors: Yuan, J.; Adamow, M.; Ginsberg, B. A.; Rasalan, T. S.; Ritter, E.; Gallardo, H. F.; Xu, Y.; Pogoriler, E.; Terzulli, S. L.; Kuk, D.; Panageas, K. S.; Ritter, G.; Sznol, M.; Halaban, R.; Jungbluth, A. A.; Allison, J. P.; Old, L. J.; Wolchok, J. D.; Gnjatic, S.
Article Title: Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab
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 thosewith undetectable CD8+ T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), aswell 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 responsesmay 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.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 108
Issue: 40
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2011-10-04
Start Page: 16723
End Page: 16728
Language: English
DOI: 10.1073/pnas.1110814108
PROVIDER: scopus
PMCID: PMC3189057
PUBMED: 21933959
DOI/URL:
Notes: --- - "Export Date: 2 November 2011" - "CODEN: PNASA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    665 Wolchok
  2. Katherine S Panageas
    329 Panageas
  3. James P Allison
    129 Allison
  4. Sacha Gnjatic
    111 Gnjatic
  5. Achim Jungbluth
    340 Jungbluth
  6. Gerd Ritter
    158 Ritter
  7. Erika Ritter
    34 Ritter
  8. Jianda Yuan
    100 Yuan
  9. Deborah Kuk
    81 Kuk
  10. Lloyd J Old
    385 Old
  11. Teresa Rasalan
    25 Rasalan
  12. Matthew J Adamow
    10 Adamow
  13. Yinyan Xu
    11 Xu