Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer.
Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer.
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发表时间：
2003
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通讯作者：
E. Solomayer;M. Feuerer;L. Bai;V. Umansky;P. Beckhove;G. Meyberg;G. Bastert;V. Schirrmacher;I. Diel
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作者：
E. Solomayer;M. Feuerer;L. Bai;V. Umansky;P. Beckhove;G. Meyberg;G. Bastert;V. Schirrmacher;I. Diel
目的：骨髓是乳腺癌患者抗肿瘤免疫记忆的特殊隔间。到目前为止，辅助全身治疗对免疫系统的影响只在外周血中研究过，而没有在骨髓中研究过。在本研究中，我们分析了激素治疗和化疗对骨髓免疫激活状态的影响。实验设计：34例乳腺癌患者在初次手术和辅助全身治疗后24个月进行骨髓抽吸。将这些患者的免疫系统与初次手术时的患者进行比较（n = 90）。三色流式细胞术通过单克隆抗体检测T细胞、自然杀伤细胞（NK）、单核/巨噬细胞和亚群的数量和激活状态。结果辅助全身治疗后患者的全部T细胞比例明显低于原发性乳腺癌患者或正常健康供者。化疗显然对naïve CD4 T细胞有特别的抑制作用，在较小程度上对记忆CD4 T细胞也有抑制作用。激素治疗对naïve和记忆性CD8 T细胞均有明显的抑制作用。辅助化疗后NK细胞（CD56）和单核/巨噬细胞（CD14）的数量迅速恢复。然而，具有潜在抗肿瘤反应性的亚群，如活化的NK细胞和NK T细胞，在化疗后长期减少。结论：这些研究结果表明，目前乳腺癌辅助治疗对骨髓免疫系统有深远而持久的负面影响。
PURPOSE Bone marrow is a special compartment for antitumor immunological memory in patients with breastcancer. Until now, the influence of adjuvant systemic therapy on the immune system has only been investigated in peripheral blood and not in bone marrow. In this study, we analyzed the effect of hormone therapy and chemotherapy on the immune activation status in bone marrow. EXPERIMENTAL DESIGN In 34 patients with breast cancer, bone marrow was aspirated 24 months after primary surgery and adjuvant systemic therapy. The immune system of these patients was compared with that of patients at the time of primary surgery (n = 90). Three-color flow cytometry was used to identify the number and activation state of T cells, natural killer (NK) cells, monocytes/macrophages, and subsets by means of a panel of monoclonal antibodies. RESULTS The proportion of all T cells was significantly lower in patients after adjuvant systemic therapy than in patients with primary breast cancer or normal healthy donors. Chemotherapy apparently had a particularly suppressive effect on naïve CD4 T cells and, to a lesser extent, on memory CD4 T cells. Hormone therapy apparently had a significant suppressive effect on both naïve and memory CD8 T cells. The numbers of NK cells (CD56) and of monocytes/macrophages (CD14) recovered rapidly after adjuvant chemotherapy. However, subpopulations with potential antitumor reactivity, such as activated NK and NK T cells, were reduced per long term after chemotherapy. CONCLUSIONS These findings suggest profound and long-lasting negative effects on the bone marrow immune system by present day adjuvant therapy in breast cancer.