Paczesny Sophie, Shi Honhgzhen, Saito Hiroaki, Mannoni Patrice, Fay Joseph, Banchereau Jacques, Palucka A Karolina
Baylor Institute for Immunology Research, Baylor University Medical Center, Dallas, Texas 75204, USA.
J Immunother. 2005 Mar-Apr;28(2):148-57. doi: 10.1097/01.cji.0000154247.97254.ef.
Improving cancer vaccines depends on assays measuring elicited tumor-specific T-cell immunity. Cytotoxic effector cells are essential for tumor clearance and are commonly evaluated using 51Cr release from labeled target cells after a short (4 hours) incubation with T cells. The authors used a tumor inhibition assay (TIA) that assesses the capacity of cytotoxic T lymphocytes (CTLs) to control the survival/growth of EGFP-labeled tumor cell lines. TIA was validated using CD8+ T cells primed in vitro against melanoma and breast cancer cells. TIA was then used to assess the CTL function of cultured CD8+ T cells isolated from patients with metastatic melanoma who underwent vaccination with peptide-pulsed CD34+ HPCs-derived DCs. After the DC vaccination, T cells from six of eight patients yielded CTLs that could inhibit the survival/growth of melanoma cells. The results of TIA correlated with killing of tumor cells in a standard 4-hour 51Cr release assay, yet TIA allowed detection of CTL activities that appeared marginal in the 51Cr release assay. Thus, TIA might prove valuable for measuring spontaneous and induced antigen-specific cytotoxic T cells.
改进癌症疫苗依赖于能够检测所引发的肿瘤特异性T细胞免疫的检测方法。细胞毒性效应细胞对于肿瘤清除至关重要，通常通过在与T细胞短时间（4小时）孵育后，测量标记靶细胞释放的51Cr来进行评估。作者使用了一种肿瘤抑制检测法（TIA），该方法评估细胞毒性T淋巴细胞（CTL）控制EGFP标记的肿瘤细胞系存活/生长的能力。使用体外针对黑色素瘤和乳腺癌细胞致敏的CD8 + T细胞对TIA进行了验证。然后，TIA被用于评估从接受肽脉冲CD34 + HPCs衍生的DC疫苗接种的转移性黑色素瘤患者中分离出的培养CD8 + T细胞的CTL功能。DC疫苗接种后，8名患者中有6名患者的T细胞产生了能够抑制黑色素瘤细胞存活/生长的CTL。TIA的结果与标准4小时51Cr释放检测中肿瘤细胞的杀伤情况相关，但TIA能够检测到在51Cr释放检测中似乎处于边缘状态的CTL活性。因此，TIA可能被证明在测量自发和诱导的抗原特异性细胞毒性T细胞方面具有价值。
