Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness.
We amplified RNAs from 63 fine needle aspiration (FNA) samples from 37 s.c. melanoma metastases from 25 patients undergoing immunotherapy for hybridization to a 6108-gene human cDNA chip. By prospectively following the history of the lesions, we could correlate transcript patterns with clinical outcome. Cluster analysis revealed a tight relationship among autologous synchronously sampled tumors compared with unrelated lesions (average Pearson's r = 0.83 and 0.7, respectively, P < 0.0003). As reported previously, two subgroups of metastatic melanoma lesions were identified that, however, had no predictive correlation with clinical outcome. Ranking of gene expression data from pretreatment samples identified approximately 30 genes predictive of clinical response (P < 0.001). Analysis of their annotations denoted that approximately half of them were related to T-cell regulation, suggesting that immune responsiveness might be predetermined by a tumor microenvironment conducive to immune recognition.
Wang
Ena
E
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland 20892, USA.
Miller
Lance D
LD
Ohnmacht
Galen A
GA
Mocellin
Simone
S
Perez-Diez
Ainhoa
A
Petersen
David
D
Zhao
Yingdong
Y
Simon
Richard
R
Powell
John I
JI
Asaki
Esther
E
Alexander
H Richard
HR
Duray
Paul H
PH
Herlyn
Meenhard
M
Restifo
Nicholas P
NP
Liu
Edison T
ET
Rosenberg
Steven A
SA
Marincola
Francesco M
FM
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000235:genetics; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies