Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients.
Distribution, patterns and prognostic impact of spontaneous antibody responses against different tumor-associated antigens (TAAs) in malignant melanoma patients are unknown so far and were investigated in this study for the first time in a large cohort at different stages of the disease, identifying new prognostic biomarkers for malignant melanoma. Serum samples from 365 melanoma patients (97 Stage I melanoma patients, 87 Stage II, 92 Stage III and 89 Stage IV) and 100 age and gender matched healthy control donors were analyzed. Samples were drawn at the time of diagnosis (Stages I-III) or at time of diagnosis of distant metastasis (Stage IV). Applying a novel multiplex assay, humoral immune responses against 29 TAAs were determined and the association between response and patient survival was investigated. Antibody responses were mainly found in melanoma patients and all tested antigens elicited immune responses in all disease stages. Antibody responses against single antigens were either associated with poor prognosis and/or shorter progression-free survival (PFS) or had no influence. While in Stages I-III significant associations were observed between an antibody response and overall survival or PFS, among Stage IV patients, no significant association was found. Multivariate analyses identified specific humoral immune responses as prognostic factors independently of age, chemotherapy and immunotherapy. Antibody responses against specific TAA in Stage I-III melanoma patients correlate with poor prognosis and/or shorter PFS. These results may help to design clinical studies in order to evaluate the potential of these responses as prognostic serological biomarkers.
Department of Medical Oncology, National Center for Tumor Diseases, Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany.
Inka
I
Zörnig
Niels
N
Halama
Justo
J
Lorenzo Bermejo
Claudia
C
Ziegelmeier
Elke
E
Dickes
Alexander
A
Migdoll
Iris
I
Kaiser
Tim
T
Waterboer
Michael
M
Pawlita
Niels
N
Grabe
Selma
S
Ugurel
Dirk
D
Schadendorf
Christine
C
Falk
Stefan B
SB
Eichmüller
Dirk
D
Jäger
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
D000951:Antigens, Neoplasm
malignant melanoma; multiplex analysis; prognosis; serum antibodies; tumor associated antigens