Rosato Antonio, Zoso Alessia, Dalla Santa Silvia, Milan Gabriella, Del Bianco Paola, De Salvo Gian Luca, Zanovello Paola
Department of Oncology and Surgical Sciences, University of Padova, Italy.
J Immunol. 2006 Feb 1;176(3):1999-2006. doi: 10.4049/jimmunol.176.3.1999.
Identification of reliable surrogate predictors for evaluation of cancer vaccine efficacy is a critical issue in immunotherapy. We analyzed quantitative and qualitative CD8+ T cell parameters in a large pool of BALB/c mice that were DNA-vaccinated against P1A self tumor-specific Ag. After immunization, mice were splenectomized and kept alive for a subsequent tumor challenge to correlate results of immune monitoring assays with tumor regression or progression in each individual animal, and to assess the prognostic value of the assays. The parameters tested were 1) percentage of in vivo vaccine-induced tumor-specific CD8+ T cells; 2) results of ELISPOT tests from fresh splenocytes; 3) percentage of tumor-specific CD8+ T cells in culture after in vitro restimulation; 4) in vitro increase of tumor-specific CD8+ T cell population expressed as fold of expansion; and 5) antitumor lytic activity of restimulated cultures. Except for the ELISPOT assay, each parameter tested was shown by univariate statistical analysis to correlate with tumor regression. However, multivariate analysis revealed that only in vitro percentage of Ag-specific CD8+ T cells was an independent prognostic factor that predicted tumor outcome. These findings should be considered in the design of new immune monitoring systems used in cancer immunotherapy studies.
确定可靠的替代预测指标以评估癌症疫苗疗效是免疫治疗中的一个关键问题。我们分析了大量经DNA疫苗接种以对抗P1A自身肿瘤特异性抗原的BALB/c小鼠的定量和定性CD8+ T细胞参数。免疫后，对小鼠进行脾切除并使其存活以进行后续肿瘤攻击，从而将免疫监测分析结果与每只动物的肿瘤消退或进展相关联，并评估这些分析的预后价值。所测试的参数包括：1）体内疫苗诱导的肿瘤特异性CD8+ T细胞百分比；2）新鲜脾细胞的ELISPOT测试结果；3）体外再刺激后培养物中肿瘤特异性CD8+ T细胞百分比；4）以扩增倍数表示的体外肿瘤特异性CD8+ T细胞群体的增加；5）再刺激培养物的抗肿瘤裂解活性。除ELISPOT分析外，单变量统计分析显示所测试的每个参数均与肿瘤消退相关。然而，多变量分析表明，只有体外Ag特异性CD8+ T细胞百分比是预测肿瘤结局的独立预后因素。在癌症免疫治疗研究中使用的新免疫监测系统设计中应考虑这些发现。
