Function but not phenotype of melanoma peptide-specific CD8 super(+) T cells correlate with survival in a multiepitope peptide vaccine trial (ECOG 1696)

• Published in: International journal of cancer 2012-08, Vol.131 (4), p.874-884
• Main Authors: Schaefer, Carsten, Butterfield, Lisa H, Lee, Sandra, Kim, Grace G, Visus, Carmen, Albers, Andreas, Kirkwood, John M, Whiteside, Theresa L
• Format: Article
• Language: English
• Subjects: CC chemokine receptors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.26481

ECOG 1696 was a Phase II multi-center trial testing vaccination with melanoma peptides, gp100, MART-1 and tyrosinase delivered alone, with GM-CSF, IFN-[alpha]2b or both cytokines to HLA-A2 super(+) patients with metastatic melanoma. Here, the frequency of circulating CD8 super(+)tetramer super(+) (tet super(+)) T cells and maturation stages of responding T cells were serially monitored and compared with baseline values in a subset of patients (n = 37) from this trial. Multiparameter flow cytometry was used to measure the frequency of CD8 super(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides. Expression of CD45RA/CCR7 on CD8 super(+)tet super(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined. Vaccine-induced changes in the CD8 super(+)tet super(+) T cell frequency and phenotype were compared with results of IFN-[gamma] ELISPOT assays and with clinical responses. The frequency of CD8 super(+)tet super(+) T cells in the circulation was increased for the melanoma peptides (p < 0.03-0.0001) but not for FLU (p < 0.9). Only gp100- and MART-1-specific T cells differentiated to CD45RA super(+)CCR7 super(-) effector/memory T cells. In contrast to the IFN-[gamma] ELISPOT frequency, previously correlated with overall survival (Kirkwood et al., Clin Cancer Res 2009; 15:1443-51), neither the frequency nor differentiation stage of CD8 super(+)tet super(+) T cells correlated with clinical responses. Delivery of GM-CSF and/or IFN-[alpha]2b had no effects on the frequency or differentiation of CD8 super(+)tet super(+), CD8+ or CD4+ T cells. Phenotypic analyses of CD8 super(+)tet super(+) T cells did not correlate with clinical responses to the vaccine, indicating that functional assessments of peptide-specific T cells are preferable for monitoring of anti-tumor vaccines.