TY - JOUR
T1 - Integrated NY-ESO-1 antibody and CD8 + T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab
AU - Yuan, Jianda
AU - Adamow, Matthew
AU - Ginsberg, Brian A.
AU - Rasalan, Teresa S.
AU - Ritter, Erika
AU - Gallardo, Humilidad F.
AU - Xu, Yinyan
AU - Pogoriler, Evelina
AU - Terzulli, Stephanie L.
AU - Kuk, Deborah
AU - Panageas, Katherine S.
AU - Ritter, Gerd
AU - Sznol, Mario
AU - Halaban, Ruth
AU - Jungbluth, Achim A.
AU - Allison, James P.
AU - Old, Lloyd J.
AU - Wolchok, Jedd D.
AU - Gnjatic, Sacha
PY - 2011/10/4
Y1 - 2011/10/4
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1110814108
DO - 10.1073/pnas.1110814108
M3 - Article
C2 - 21933959
AN - SCOPUS:80053648839
SN - 0027-8424
VL - 108
SP - 16723
EP - 16728
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 40
ER -