Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Int J Cancer. 2012 Aug 15;131(4):874-84. doi: 10.1002/ijc.26481. Epub 2012 Jan 11.
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-α2b or both cytokines to HLA-A2(+) patients with metastatic melanoma. Here, the frequency of circulating CD8(+) tetramer(+) (tet(+) ) 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(+) T cells specific for gp100, MART-1, tyrosinase and influenza (FLU) peptides. Expression of CD45RA/CCR7 on CD8(+) tet(+) T cells and CD25, CD27, CD28 on all circulating T cells was determined. Vaccine-induced changes in the CD8(+) tet(+) T cell frequency and phenotype were compared with results of IFN-γ ELISPOT assays and with clinical responses. The frequency of CD8(+) tet(+) 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(+) CCR7(-) effector/memory T cells. In contrast to the IFN-γ 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(+) tet(+) T cells correlated with clinical responses. Delivery of GM-CSF and/or IFN-α2b had no effects on the frequency or differentiation of CD8(+) tet(+) , CD8+ or CD4+ T cells. Phenotypic analyses of CD8(+) tet(+) 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.
ECOG 1696 是一项 II 期多中心试验，旨在测试黑色素瘤肽、gp100、MART-1 和酪氨酸酶的疫苗接种，这些肽单独使用，或与 GM-CSF、IFN-α2b 或两种细胞因子联合使用，用于 HLA-A2(+)转移性黑色素瘤患者。在这里，我们对该试验的一部分患者（n = 37）进行了连续监测，并与基线值进行了比较，以检测循环 CD8(+)四聚体(+)（tet(+)）T 细胞的频率和反应性 T 细胞的成熟阶段。多参数流式细胞术用于测量 gp100、MART-1、酪氨酸酶和流感（FLU）肽特异性 CD8(+)T 细胞的频率。测定 CD8(+)tet(+)T 细胞上的 CD45RA/CCR7 表达和所有循环 T 细胞上的 CD25、CD27、CD28。将 CD8(+)tet(+)T 细胞频率和表型的疫苗诱导变化与 IFN-γ ELISPOT 检测结果和临床反应进行比较。与 IFN-γ ELISPOT 频率（先前与总生存相关（Kirkwood 等人，Clin Cancer Res 2009；15:1443-51））相比，循环中 CD8(+)tet(+)T 细胞的频率增加了黑色素瘤肽（p < 0.03-0.0001），但 FLU 肽（p < 0.9）没有增加。只有 gp100 和 MART-1 特异性 T 细胞分化为 CD45RA(+)CCR7(-)效应/记忆 T 细胞。与之前与总生存相关（Kirkwood 等人，Clin Cancer Res 2009；15:1443-51）的 IFN-γ ELISPOT 频率不同，循环中 CD8(+)tet(+)T 细胞的频率或分化阶段均与临床反应无关。GM-CSF 和/或 IFN-α2b 的递送对 CD8(+)tet(+)、CD8+或 CD4+T 细胞的频率或分化没有影响。CD8(+)tet(+)T 细胞的表型分析与疫苗的临床反应无关，表明肽特异性 T 细胞的功能评估更适合监测抗肿瘤疫苗。
