Tumor Immunity in Perforin-Deficient Mice: A Role for CD95 (Fas/APO-1)1
Tumor Immunity in Perforin-Deficient Mice: A Role for CD95 (Fas/APO-1)1
复制标题
穿孔素缺陷小鼠的肿瘤免疫：CD95 (Fas/APO-1)1 的作用
作者：
D. Rosen;Jie;S. Keidar;I. Markon;R. Orda;G. Berke
CTL和NK细胞使用两种不同的杀伤途径：1)穿孔素和颗粒酶；2)CD95L/CD95介导。前者需要效应分子(CTL或NK)表达穿孔素，而后者需要靶点表达CD95(Fas/APO-1)。我们通过研究穿孔素缺陷小鼠对进展性C57BL/6 Lewis肺癌3LL的免疫作用，研究了这两个因素在肿瘤免疫监测中的作用，该细胞在体外培养时不表达CD95。结果意外地表明，CTL/NK的穿孔素非依赖性CD95L/CD95通路分别对来源于3LL肿瘤的D122和Kb39.5(39.5)高、低转移亚系起作用。虽然在培养的D122和39.5细胞上没有检测到膜结合的CD95，但当肿瘤在体内生长时，D122和39.5上的CD95表达都显著上调。另外三种肿瘤：Lf−、BW和P815，注射到同基因和同种异体小鼠中，CD95的表达也有类似的增强。体内放置的肿瘤细胞上CD95表达上调的发现表明，在肿瘤生长的早期阶段，基于CD95的机制在肿瘤免疫中发挥作用。因此，正如先前报道的那样，CD95在肿瘤进展过程中表达的进行性下调可能确实是一种逃避机制。综上所述，这些结果表明CD95依赖的、穿孔素不依赖的免疫对某些肿瘤具有作用。
CTL and NK cells use two distinct cytocidal pathways: 1) perforin and granzyme based and 2) CD95L/CD95 mediated. The former requires perforin expression by the effectors (CTL or NK), whereas the latter requires CD95 (Fas/APO-1) expression by the target. We have investigated how these two factors contribute to tumor immune surveillance by studying the immunity of perforin-deficient mice against the progressor C57BL/6 Lewis lung carcinoma 3LL, which expresses no CD95 when cultured in vitro. Unexpectedly, the results indicated that the perforin-independent CD95L/CD95 pathway of CTL/NK plays a role in acting against D122 and Kb39.5 (39.5) high and low metastatic sublines, respectively, derived from the 3LL tumor. Although no membrane-bound CD95 was detected on cultured D122 and 39.5 cells, surface CD95 expression on both D122 and 39.5 was considerably up-regulated when the tumors were grown in vivo. A similarly enhanced expression of CD95 was observed with three additional tumors; LF−, BW, and P815, injected into syngeneic and allogeneic mice. The finding of up-regulated CD95 expression on tumor cells placed in vivo suggests that a CD95-based mechanism plays a role in tumor immunity at early stages of tumor growth. Consequently, the progressive down-regulation of CD95 expression during tumor progression may indeed be an escape mechanism as previously reported. Together, these results suggest a role for CD95-dependent, perforin-independent immunity against certain tumors.
影响因子：
20.3
作者：
Bradley, M;Zeytun, A;Nagarkatti, M
通讯作者：
Nagarkatti, M
Fas 裂解途径在无穿孔素 CTL 杂交瘤中的作用。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Walsh,CM;Glass,AA;Chiu,V;Clark,WR
通讯作者：
Clark,WR
DOI：
10.1073/pnas.91.23.10854
发表时间：
1994-11-08
影响因子：
11.1
作者：
WALSH, CM;MATLOUBIAN, M;CLARK, WR
通讯作者：
CLARK, WR