The ability of two Listeria monocytogenes vaccines targeting human papillomavirus-16 E7 to induce an antitumor response correlates with myeloid dendritic cell function
The ability of two Listeria monocytogenes vaccines targeting human papillomavirus-16 E7 to induce an antitumor response correlates with myeloid dendritic cell function
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DOI：
10.4049/jimmunol.172.10.6030
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Paterson, Y
中科院分区：
文献类型：
--
作者：
Peng, XH;Hussain, SF;Paterson, Y
我们实验室以前的工作已经表明，Lm-LLO-E7诱导类似于75%的已建立的TC-1肿瘤的完全消退，而Lm-E7仅减缓此类肿瘤的生长。在这项研究中，我们检查了Lm-LLO-E7与Lm-E7对APC的影响。我们推测，这两种疫苗的抗肿瘤疗效的差异是由于这些载体中的每一个使未成熟树突状细胞（DC）有效的APC在MHC II类或共刺激分子表达方面的能力。我们还研究了这些载体刺激DC产生细胞因子的能力。两种载体均诱导IL-12和TNF-α，但只有Lm-LL 0-E7诱导DC产生IL-2。Lm-LLO-E7还诱导DC上的MHC 11类分子、CD 40和B7共刺激分子（CD 86、B7-H1和B7-DC）的水平显著高于Lm-E7。有趣的是，在Lm-LLO-E7感染后观察到CD 11 c（+）细胞从CD 86（低）向CD 86（高）的转变。对于B7-H1和B7-DC分子也观察到类似的位移。此外，Lm-LL 0-E7而不是Lm-E7脉冲的DC刺激初始T细胞增殖。这些结果表明Lm-LL 0-E7在诱导DC成熟方面比Lm-E7更有效。这种作用不依赖于E7 Ag，因为Lm-LLO-NP以及Lm-LLO-NP和Lm-E7的混合物诱导与Lm-LLO-E7相同的DC表型变化。总之，DC表达的变化与这两种疫苗之间的抗肿瘤功效的差异密切相关。
Previous work from our laboratory has shown that Lm-LLO-E7 induces complete regression of similar to75% of established TC-1 tumors, whereas Lm-E7 only slows the growth of such tumors. In this study, we examine the effects of Lm-LLO-E7 vs Lm-E7 on APCs. We hypothesize that the difference in antitumor efficacy of the two vaccines is due to the ability of each of these vectors to render immature dendritic cells (DCs) effective APCs in terms of MHC class II or costimulatory molecule expression. We also examine the ability of these vectors to stimulate cytokine production by DCs. Both vectors induced IL-12 and TNF-alpha, but only Lm-LLO-E7 induced IL-2 production by DCs. Lm-LLO-E7 also induced significantly higher levels of MHC class 11 molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7. Interestingly, a shift of CD11c(+) cells from CD86(low) to CD86(high) is observed post-Lm-LLO-E7 infection. A similar shift is also observed for B7-H1 and B7-DC molecules. Moreover, Lm-LLO-E7, but not Lm-E7-pulsed DCs, stimulate naive T cell proliferation. These results indicate that Lm-LLO-E7 is more effective than Lm-E7 at inducing DC maturation. This effect is independent of the E7 Ag, because Lm-LLO-NP, and a mixture of Lm-LLO-NP and Lm-E7 induce the same changes in DC phenotype as Lm-LLO-E7. Taken together, the changes in DC expression correlate well with the differences in antitumor efficacy between these two vaccines.