Boom M, Pollock R E, Shenk R R, Stanford S
Department of General Surgery, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston.
Invasion Metastasis. 1988;8(2):118-32.
Natural killer (NK) cells may be important in the control of circulating tumor emboli. Because of this, the suppression of natural killer cell cytotoxicity (NKCC) observed with progressive tumor burden is a concern relative to the treatment of solid tumors. Our study examines the interplay between tumor progression, elaboration of metastases, and NKCC. Mice inoculated with Lewis lung carcinoma (3LL) cells developed visible primary tumors by day 6 of tumor bearing. This tumor burden appeared to be associated with a progressive decrease in NKCC beginning after day 6 of tumor bearing. Significant splenomegaly was observed beginning by day 12. Rapidly reproducing tumor cells take up 125I-labeled 5-iodo-2'-deoxyuridine (125I-IUDR) in lieu of thymidine more readily than normal cells. Intraperitoneal injection of the labeled IUDR allowed the identification of possible pulmonary metastatic activity earlier in the tumor progression sequence than has previously been possible using standard staining procedures. A significantly increased level of lung 125I-IUDR uptake was observed in the lung beginning after day 6 of tumor bearing; this increase in 125I-IUDR uptake began at the same time as the tumor burden impairment of NKCC. Successful implantation of tumor emboli may occur very early in experimental tumor burden systems, when measurable antitumor immune effector mechanisms are not yet massively suppressed. Antitumor immunotherapy programs may therefore need to be targeted to these earlier points of tumor bearing.
自然杀伤（NK）细胞可能在控制循环肿瘤栓子方面发挥重要作用。正因如此，随着肿瘤负荷的增加，自然杀伤细胞细胞毒性（NKCC）受到抑制，这对于实体瘤的治疗而言是一个值得关注的问题。我们的研究探讨了肿瘤进展、转移形成与NKCC之间的相互作用。接种Lewis肺癌（3LL）细胞的小鼠在荷瘤第6天时出现可见的原发性肿瘤。这种肿瘤负荷似乎与荷瘤第6天之后NKCC的逐渐降低有关。从第12天开始观察到明显的脾肿大。快速增殖的肿瘤细胞比正常细胞更容易摄取125I标记的5-碘-2'-脱氧尿苷（125I-IUDR）以替代胸苷。与使用标准染色程序相比，腹腔注射标记的IUDR能够在肿瘤进展序列中更早地识别可能的肺转移活性。在荷瘤第6天之后，观察到肺中125I-IUDR摄取水平显著增加；125I-IUDR摄取的增加与NKCC的肿瘤负荷损伤同时开始。在实验性肿瘤负荷系统中，当可测量的抗肿瘤免疫效应机制尚未受到大规模抑制时，肿瘤栓子可能在很早的时候就成功植入。因此，抗肿瘤免疫治疗方案可能需要针对这些较早的荷瘤阶段。
