Department of Gynecology and Obstetrics, University Hospital of Heidelberg, Germany.
Cancer Immunol Immunother. 2010 Mar;59(3):479-86. doi: 10.1007/s00262-009-0801-9. Epub 2009 Dec 2.
Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-gamma producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-gamma EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A(*0201)-restricted peptides from the tumor-associated antigens MUC1, Hpa(16-24) and Hpa(183-191) was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM.
在大多数乳腺癌患者的骨髓（BM）中可检测到肿瘤特异性记忆 T 细胞。在体外，它们可以被重新激活为 IFN-γ产生的细胞毒性效应细胞，并在 NOD/SCID 小鼠中通过自体树突状细胞（DC）的特异性再刺激来排斥自体、异种移植的肿瘤。在这项研究中，我们通过使用未刺激的 T 细胞和自体 DC 进行短期 IFN-γ Elispot 测定，在总共 129 名原发性手术乳腺癌患者中的 56 名患者中证实了存在特异性肿瘤反应性 BM 记忆 T 细胞。我们观察到，主要是患有转移性疾病的患者（P=0.011）或外周血中肿瘤标志物 CA 15-3 浓度升高的患者（P=0.004）存在肿瘤反应性 BM 记忆 T 细胞。对 HLA-A(*0201)-限制性肽的记忆 T 细胞反应来自肿瘤相关抗原 MUC1、Hpa(16-24)和 Hpa(183-191)，也在 CA 15-3 浓度升高的患者中特别检测到（P<0.05）。总之，这些数据表明，肿瘤来源抗原的全身存在促进了人类 BM 中肿瘤特异性细胞免疫反应的诱导。
