Basse P H, Herberman R B, Hokland M E, Goldfarb R H
Pittsburgh Cancer Institute, University of Pittsburgh, Pa.
Nat Immun. 1992 Jul-Aug;11(4):193-202.
The ability of LAK and adherent LAK (A-LAK) cells to migrate to and localize into tumors might be a limiting factor for the efficacy of adoptive immunotherapy. Employing different routes of inoculation of A-LAK cells labeled with 125IUdR, we have investigated how murine A-LAK cells circulate in the bloodstream and localize into various tissues. After intravenous injection, most of the A-LAK cells migrated to the lungs with less than 15% redistributing to other organs. Following left ventricular inoculation, after which the injected cells do not have to pass the lung capillaries before reaching other organs, higher numbers of A-LAK cells were found in liver, carcass, kidney and gut compared to intravenous injection. However, most of the A-LAK cells were cleared from these organs within 24 h, and surprisingly at this time the overall survival of the injected A-LAK cells was not more than 10-20% regardless of the route of injection. We found that a substantial accumulation of A-LAK cells in the liver could be achieved only when the cells were injected directly into the portal vein. Following this route of administration, more than 40% of the injected A-LAK cells were still in the liver at 24 h, whereas only 3-5% had redistributed to other organs. Our data suggest that A-LAK cells circulate inefficiently and survive poorly following systemic administration. However, enhanced accumulation of these cells in a particular organ might be achieved by direct administration of the A-LAK cells into the vessels feeding the organ.
LAK细胞和贴壁LAK（A-LAK）细胞迁移至肿瘤并在肿瘤中定位的能力可能是过继性免疫治疗疗效的一个限制因素。我们采用不同途径接种用¹²⁵IUdR标记的A-LAK细胞，研究了小鼠A-LAK细胞如何在血流中循环并在各种组织中定位。静脉注射后，大多数A-LAK细胞迁移至肺部，重新分布至其他器官的细胞不到15%。左心室接种后，注入的细胞在到达其他器官之前不必经过肺毛细血管，与静脉注射相比，在肝脏、胴体、肾脏和肠道中发现的A-LAK细胞数量更多。然而，大多数A-LAK细胞在24小时内从这些器官中清除，令人惊讶的是，此时无论注射途径如何，注入的A-LAK细胞的总体存活率不超过10%-20%。我们发现，只有将细胞直接注入门静脉，才能在肝脏中实现A-LAK细胞的大量积聚。采用这种给药途径，24小时时超过40%的注入A-LAK细胞仍在肝脏中，而只有3%-5%重新分布至其他器官。我们的数据表明，全身给药后A-LAK细胞循环效率低下且存活不佳。然而，通过将A-LAK细胞直接注入为该器官供血的血管中，可能会增强这些细胞在特定器官中的积聚。
