自然杀伤细胞
维基百科,自由的百科全书
自然杀伤细胞是一种細胞質中具有大顆粒的细胞,也称NK细胞。因為其非專一性的細胞毒殺作用而被命名。沒有T細胞B細胞所具的受體,不會進行受體的基因重組。但仍具有一些特殊受體,可以活化或抑制其作用。佔循環中淋巴細胞族群的5-10%。和殺死腫瘤細胞有關,可利用分泌穿孔素及腫瘤壞死因子,摧毀目標細胞。
Virulizin, a natural extract of low organic weight molecules, has shown promise in Phase I/II studies of pancreatic adenocarcinoma, and in melanoma. NK cell function is believed to be a main mediator of pharmacologic activity. OBJECTIVE: To determine if Virulizin produces increased NK cell activity in human tumor xenografted in mice. METHODS: CD-1 nude mice harboring C8161 human melanoma or Capan-1 pancreatic tumor xenografts were treated with Virulizin and tumor cells were subjected to flow cytometric analyses using NK cell-specific antibodies. NK cell-deficient SCID/beige mice were used to assess the contributions of NK cells in Virulizin-mediated C8161 tumor suppression. Finally, the extent of NK cell infiltration to and in vivo efficacy against C8161 tumors were evaluated in CD-1 nude mice depleted of macrophages. RESULTS: FACS analyses showed that Virulizin treatment results in increased NK cell infiltration into tumors (59.4 to 116.0%). The anti-tumor effects of Virulizin are significantly compromised in NK cell-deficient mice. Furthermore, selective depletion of macrophages abrogates NK cell infiltration to the tumor and significantly compromises antitumor activity of Virulizin (P=0.1632). CONCLUSION: The current studies implicate macrophage-mediated NK cell activation/recruitment in the mechanism of action of Virulizin. These results are consistent with a Phase II study of pancreatic cancer in which Virulizin produced increased NK cell activity compared to base-line levels in a sub-group of patients showing the best response (survival) to Virulizin. Low NK cell activity may be a risk factor for malignancy or metastases and a negative prognostic indicator in various cancers. To evaluate further the utility of NK cell function as a biologic marker of clinical response, NK cell function and other immune parameters are being assessed in an ongoing Phase III trial in advanced pancreatic cancer as a first line combination therapy with Gemcitabine. NK cell function will be correlated with survival and other clinical response parameters