Thomas W D, Hersey P
Department of Surgery, John Hunter Hospital, Newcastle, Australia.
Int J Cancer. 1998 Jan 30;75(3):384-90. doi: 10.1002/(sici)1097-0215(19980130)75:3<384::aid-ijc10>3.0.co;2-9.
Previous studies have shown that CD4 T cells are associated with regression in primary melanoma and rejection of tumors in adoptive transfer models. The mechanism by which they mediate their anti-tumor effects remains unclear, and some studies have suggested that Fas ligand (FasL)/Fas interactions were involved. In the present study, we have examined the cytotoxic mechanism involved in CD4 T-cell killing of melanoma cells and, in particular, the role of FasL/Fas interactions in this killing. We show that the CD4 T cells in 4 clones of T cells induced apoptosis in autologous melanoma cells by MHC-restricted mechanisms but lysed an allogeneic melanoma cell by a non-apoptotic mechanism. Melanoma cells expressed both Fas and FasL, but killing of melanoma cells did not involve Fas/FasL interactions. This was shown by a lack of correlation between Fas expression and susceptibility to lysis and by failure of a monoclonal antibody to Fas to block killing by the CD4 T cells, though the latter expressed FasL. Recombinant FasL did not induce killing of melanoma cells.
先前的研究表明，CD4 T细胞与原发性黑色素瘤的消退以及过继性转移模型中肿瘤的排斥有关。它们介导抗肿瘤作用的机制尚不清楚，一些研究表明Fas配体（FasL）/Fas相互作用参与其中。在本研究中，我们研究了CD4 T细胞杀伤黑色素瘤细胞所涉及的细胞毒性机制，特别是FasL/Fas相互作用在这种杀伤中的作用。我们发现，4个T细胞克隆中的CD4 T细胞通过MHC限制机制诱导自体黑色素瘤细胞凋亡，但通过非凋亡机制裂解异基因黑色素瘤细胞。黑色素瘤细胞同时表达Fas和FasL，但黑色素瘤细胞的杀伤并不涉及Fas/FasL相互作用。这通过Fas表达与裂解敏感性之间缺乏相关性以及抗Fas单克隆抗体未能阻断CD4 T细胞的杀伤作用得以证明，尽管后者表达FasL。重组FasL并未诱导黑色素瘤细胞的杀伤。
