Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases.
Accumulation of adoptively transferred adherent, lymphokine-activated killer cells in murine metastases.
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DOI：
10.1084/jem.174.2.479
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发表时间：
1991-08-01
期刊：
影响因子：
--
通讯作者：
Goldfarb RH
中科院分区：
文献类型：
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作者：
Basse P;Herberman RB;Nannmark U;Johansson BR;Hokland M;Wasserman K;Goldfarb RH
虽然淋巴因子激活的杀伤（LAK）/粘附的淋巴因子激活的杀伤（A-LAK）细胞和肿瘤细胞之间的紧密接触被认为是引发导致肿瘤细胞溶解的事件的先决条件，但仍必须获得这些效应细胞在体内浸润肿瘤或肿瘤转移的能力的明确证据。在本研究中，我们报告了一个显着比例的过继转移的A-LAK细胞，荧光染料标记的识别，积累在肺和肝转移的B16黑色素瘤，MCA 102肉瘤和刘易斯肺癌线。因此，5- 10倍高的A-LAK细胞数被发现在恶性病变相比，周围的正常组织。静脉注射中等数量的A-LAK细胞（15 × 106）后，浸润似乎非常不均匀。然而，在过继转移4500万A-LAK细胞后，在大多数转移瘤中观察到高于1：1的A-LAK细胞/肿瘤细胞比率。令人惊讶的是，大约5%的肺转移似乎完全抵抗浸润，即使相邻的转移高度浸润。虽然在静脉内注射后观察到肺转移的大量浸润，但仅在门静脉内注射A-LAK细胞后观察到肝转移的显著浸润，表明静脉内注射的A-LAK细胞通过肺毛细血管的运输受损。这些结果提供了直接证据，即A-LAK细胞在适当的给药途径下具有迁移到不同来源的小鼠肿瘤并严重浸润转移灶的潜力。
While close contact between lymphokine-activated killer (LAK)/adherent, lymphokine-activated killer (A-LAK) cells and tumor cells is believed to be a prerequisite for initiating the events leading to tumor cell lysis, clear evidence for the ability of these effector cells to infiltrate tumors or tumor metastases in vivo still has to be obtained. In the present study, we report that a significant fraction of adoptively transferred A-LAK cells, labeled with fluorochromes for identification, accumulates in lung and liver metastases of the B16 melanoma, the MCA 102 sarcoma and the Lewis lung carcinoma lines. Thus, 5- to 10-fold higher numbers of A-LAK cells were found in the malignant lesions compared to the surrounding normal tissue. The infiltration seemed very heterogeneous after intravenous injection of moderate numbers of A-LAK cells (15 x 10(6)). However, after adoptive transfer of 45 million A-LAK cells, an A-LAK cell/tumor cell ratio higher than 1:1 in most metastases was observed. Surprisingly, approximately 5% of the lung metastases seemed totally resistant to infiltration even though neighboring metastases were highly infiltrated. While substantial infiltration of lung metastases was seen after i.v. injection, significant infiltration of liver metastases was seen only after intraportal injection of the A-LAK cells indicating impaired traffic of intravenous injected A-LAK cells through the lung capillaries. These results present direct evidence that A-LAK cells, upon a proper route of administration, have the potential to migrate to and heavily infiltrate metastases from murine tumors of different origin.