EblacZ tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells.
EblacZ tumor dormancy in bone marrow and lymph nodes: active control of proliferating tumor cells by CD8+ immune T cells.
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发表时间：
1998-12
期刊：
影响因子：
11.2
通讯作者：
Markus G. Müller;F. Gounari;Sophia Prifti;Hans Jörg Hacker;Volker Schirrmacher;K. Khazaie
中科院分区：
文献类型：
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作者：
Markus G. Müller;F. Gounari;Sophia Prifti;Hans Jörg Hacker;Volker Schirrmacher;K. Khazaie
一个定义明确的lacZ基因标记DBA/2淋巴瘤（EblacZ）被用来研究宿主免疫反应在控制肿瘤传播、持续以及转移中的作用。在sc和耳内接种的小鼠中，少量EblacZ细胞归巢到骨髓和淋巴结。骨髓驻留肿瘤细胞的频率不随原发肿瘤的生长或多次接种肿瘤细胞而改变。骨髓肿瘤细胞表达增殖相关的Ki67抗原，并在CD8+缺失时扩增。相比之下，接种nu/nu或严重联合免疫缺陷小鼠或免疫抑制的DBA/2小鼠可导致EblacZ细胞在骨髓中快速生长并转移到其他器官。移植来自EblacZ免疫的MHC同源或同基因DBA/2供者的骨髓，而不是来自幼稚供者的骨髓，可以保护sc接种的DBA/2小鼠。在骨髓移植前，体外清除CD8+ T细胞可消除保护作用。这些实验表明，骨髓和淋巴结是免疫系统控制潜在致命肿瘤细胞处于休眠状态的特权部位。转移可能是这种免疫控制失效的结果。
A well-defined lacZ gene tagged DBA/2 lymphoma (EblacZ) was used to examine the role of host immune responses in controlling tumor dissemination and persistence, as well as metastasis. In s.c. and intra-ear pinna-inoculated mice, low numbers of EblacZ cells homed to the bone marrow and lymph nodes. The frequency of bone marrow-residing tumor cells did not change with the growth of primary tumor or with multiple inoculations of tumor cells. The bone marrow-residing tumor cells expressed the proliferation-associated Ki67 antigen and expanded upon CD8+ depletion. In contrast, inoculation of nu/nu or severe combined immunodeficiency mice or of immune-suppressed DBA/2 mice led to the rapid outgrowth of EblacZ cells in the bone marrow and their metastasis to other organs. Transfer of bone marrow from EblacZ immunized MHC congenic or syngeneic DBA/2 donors, but not from naive donors, protected s.c.-inoculated DBA/2 mice. Protection was abrogated by in vitro depletion of CD8+ T cells prior to transfer of bone marrow. These experiments show that bone marrow and lymph nodes are privileged sites where potentially lethal tumor cells are controlled in a dormant state by the immune system. Metastasis may be a consequence of the breakdown of this immune control.