Morecki S, Pugatsch T, Levi S, Moshel Y, Slavin S
Department of Bone-Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Int J Cancer. 1996 Jan 17;65(2):204-8. doi: 10.1002/(SICI)1097-0215(19960117)65:2<204::AID-IJC13>3.0.CO;2-D.
Immunity to murine B-cell leukemia/lymphoma (BCL1) induced by multiple injections with irradiated tumor cells, prevented leukemia development in primary and adoptive transfer recipients despite long-lasting persistence of residual tumor cells. Detection of dormant BCL1 cells was carried out by PCR analysis using the VH-rearranged DNA sequence as a BCL1 clonal marker. Dormant tumor cells were detected > 250 days following immunity induction in 40% of spleens from healthy immune mice having no detectable symptoms of disease. Tumor dormancy was not abrogated by adoptive transfer of BCL1-containing splenocytes into syngeneic recipients, indicating that cell-mediated anti-tumor immunity contributes to maintenance of the tumor dormant state and prevents renewed tumor-cell growth. Splenocytes but not sera from immune mice conferred specific radiosensitive protection from a lethal dose of BCL1 cells included in cell mixtures transferred to secondary recipients. A therapeutic effect of transferred immune splenocytes was shown in BCL1-bearing mice, which remained disease-free for > 200 days after inoculation; nevertheless, dormant BCL1 cells were detected by PCR analysis in some of the surviving mice. Our results suggest that an efficient tumor-cell vaccine can lead to induction of tumor dormancy that can be maintained by a cell-derived mechanism for a long period of time.
多次注射经辐照的肿瘤细胞所诱导的对小鼠B细胞白血病/淋巴瘤（BCL1）的免疫，可防止原发性和过继性转移受体发生白血病，尽管残留肿瘤细胞会长期持续存在。通过使用重排的VH DNA序列作为BCL1克隆标志物的PCR分析来检测休眠的BCL1细胞。在诱导免疫后250天以上，在40%没有可检测到疾病症状的健康免疫小鼠脾脏中检测到了休眠肿瘤细胞。将含有BCL1的脾细胞过继转移到同基因受体中，并没有消除肿瘤休眠，这表明细胞介导的抗肿瘤免疫有助于维持肿瘤休眠状态，并防止肿瘤细胞重新生长。免疫小鼠的脾细胞而非血清，能对转移到二级受体的细胞混合物中包含的致死剂量的BCL1细胞提供特异性的放射敏感保护。在携带BCL1的小鼠中显示了转移的免疫脾细胞的治疗效果，这些小鼠在接种后200多天内保持无病状态；然而，通过PCR分析在一些存活小鼠中检测到了休眠的BCL1细胞。我们的结果表明，一种有效的肿瘤细胞疫苗可以导致肿瘤休眠的诱导，这种休眠可以通过一种细胞衍生机制长期维持。
