Phillips N C
Montreal General Hospital Research Institute, Department of Medicine, McGill University, Quebec, Canada.
Cancer Metastasis Rev. 1989 Dec;8(3):231-52. doi: 10.1007/BF00047339.
Kupffer cells, tissue-fixed macrophages located in the sinusoids of the liver, represent the highest concentration of mononuclear phagocytes in the body. Their ability to act as scavengers of particulate material in the blood has given rise to speculation that they play a role in controlling hepatic metastases derived from blood-borne tumor cells. Circumstantial evidence for such a role has been obtained from animal studies where Kupffer cell function has been compromised or inhibited, and from anecdotal clinical observations. Current evidence suggests that Kupffer cells are capable of nonspecifically eliminating some circulating tumor cells from the circulation via phagocytosis. This surveillance mechanism would appear to be limited in capacity, and subject to a number of external factors. Recent studies have demonstrated that Kupffer cells can be activated to a tumoricidal state via the administration of biological response modifiers such as gamma interferon or muramyl peptides. The localization of liposomes within Kupffer cells after systemic administration has provided a considerable stimulus for the efficient targeting of macrophage-activating compounds to these cells. Such therapeutic intervention, while capable of inducing Kupffer cell tumoricidal activity in situ and inhibiting tumor growth, is limited with respect to the location of the tumor cells (sinusoidal versus parenchymal) and to the size of the metastatic nodule. Therapeutic intervention using liposomes containing macrophage-activating agents may only be of benefit in patients with minimal tumor load who are at risk for hepatic metastases, rather than those patients who already have clinically detectable liver tumors.
库普弗细胞是位于肝脏窦状隙的组织固定巨噬细胞，是体内单核吞噬细胞最密集的部位。它们作为血液中颗粒物质清除剂的能力引发了一种推测，即它们在控制血源性肿瘤细胞引起的肝转移中发挥作用。这种作用的间接证据来自于库普弗细胞功能受损或受抑制的动物研究以及临床轶事观察。目前的证据表明，库普弗细胞能够通过吞噬作用非特异性地从循环中清除一些循环肿瘤细胞。这种监测机制的能力似乎有限，并且受到许多外部因素的影响。最近的研究表明，通过给予生物反应调节剂如γ干扰素或胞壁酰肽，库普弗细胞可以被激活到杀肿瘤状态。全身给药后脂质体在库普弗细胞内的定位为将巨噬细胞激活化合物有效靶向这些细胞提供了相当大的刺激。这种治疗干预虽然能够在原位诱导库普弗细胞的杀肿瘤活性并抑制肿瘤生长，但在肿瘤细胞的位置（窦状隙与实质）和转移结节的大小方面受到限制。使用含有巨噬细胞激活剂的脂质体进行治疗干预可能仅对有肝转移风险且肿瘤负荷最小的患者有益，而不是对那些已经有临床可检测肝肿瘤的患者有益。
