Feuerer M, Rocha M, Bai L, Umansky V, Solomayer E F, Bastert G, Diel I J, Schirrmacher V
Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
Int J Cancer. 2001 Apr 1;92(1):96-105.
Previous studies with animal tumors showed that bone marrow (BM) is a privileged site where potentially lethal tumor cells are controlled in a dormant state by the immune system. Here, we investigated BM of breast cancer patients with respect to tumor cell content, immune activation status and memory T-cell content. BM-derived cells from primary operated breast cancer patients (n = 90) were compared with those from healthy donors (n = 10) and also with cells from respective blood samples. Cytokeratin 19-positive tumor cells were detected by nested polymerase chain reaction. Three-color flow cytometry was used to identify numbers and activation state of T cells, natural killer (NK) cells, monocytes/macrophages and subsets by a panel of monoclonal antibodies (mAbs). The proportion of memory T cells among the CD4 and CD8 T cells was much higher in BM of cancer patients than in healthy donors (p < 0.001). The extent of memory T-cell increase was related to the size of the primary tumor. Patient-derived BM memory CD8 T cells could be shown to contain specific HLA-A2/Her-2/neu(369-377) tetramer binding cells. Patients with disseminated tumor cells in their BM had more memory CD4 T cells and more CD56(+) CD8(+) cells than patients with tumor cell-negative BM. Only some of the immunological changes seen in BM samples of cancer patients were also detectable in peripheral blood samples. Our hypothesis that BM is a special compartment for immunological memory and tumor dormancy is supported by the above findings. The overall results reveal that BM is a valuable additional compartment for immune diagnosis in pathological conditions and possibly for follow-up treatment strategies.
先前对动物肿瘤的研究表明，骨髓是一个特殊的部位，潜在致死性肿瘤细胞在此处于休眠状态并受到免疫系统的控制。在此，我们针对肿瘤细胞含量、免疫激活状态和记忆性T细胞含量，对乳腺癌患者的骨髓进行了研究。将初次手术的乳腺癌患者（n = 90）的骨髓来源细胞与健康供体（n = 10）的骨髓来源细胞进行比较，同时也与各自血液样本中的细胞进行比较。通过巢式聚合酶链反应检测细胞角蛋白19阳性肿瘤细胞。采用三色流式细胞术，通过一组单克隆抗体（mAb）鉴定T细胞、自然杀伤（NK）细胞、单核细胞/巨噬细胞及其亚群的数量和激活状态。癌症患者骨髓中CD4和CD8 T细胞中的记忆性T细胞比例远高于健康供体（p < 0.001）。记忆性T细胞增加的程度与原发肿瘤的大小有关。患者来源的骨髓记忆性CD8 T细胞可显示含有特异性HLA-A2/Her-2/neu(369 - 377)四聚体结合细胞。骨髓中存在播散性肿瘤细胞的患者比肿瘤细胞阴性的患者具有更多的记忆性CD4 T细胞和更多的CD56(+) CD8(+)细胞。癌症患者骨髓样本中出现的一些免疫变化在外周血样本中也可检测到。上述发现支持了我们的假设，即骨髓是免疫记忆和肿瘤休眠的特殊区域。总体结果表明，骨髓是病理状态下免疫诊断以及可能的后续治疗策略中一个有价值的额外区域。
