Interferon γ-induced intratumoral expression of CXCL9 alters the local distribution of T cells following immunotherapy with Listeria monocytogenes.
Interferon γ-induced intratumoral expression of CXCL9 alters the local distribution of T cells following immunotherapy with Listeria monocytogenes.
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DOI：
10.4161/onci.25752
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发表时间：
2013-08-01
期刊：
影响因子：
7.2
通讯作者：
Paterson Y
中科院分区：
文献类型：
--
作者：
Guirnalda P;Wood L;Goenka R;Crespo J;Paterson Y
基于单核细胞增生李斯特菌的抗癌疫苗诱导肿瘤消退的能力取决于恶性细胞对干扰素γ（IFNγ）的反应性。IFNγ的抑制限制了T细胞向接种疫苗的小鼠的肿瘤的募集。我们假设免疫球蛋白。单核细胞增多症诱导IFNγ依赖性趋化因子的产生，所述趋化因子调节肿瘤浸润性T细胞的迁移。为了进一步了解这个问题，我们检测了一个可移植的人乳头瘤病毒（HPV）永生化小鼠肿瘤模型（TC-1）在给予L。基于单核细胞生成的免疫抑制剂，其表达来自HPV-16的E7。在这里，我们报告说，管理L。基于单核细胞生成素的抗癌疫苗增加了肿瘤对趋化因子（C-X-C基序）配体9（CXCL 9）和CXCL 10的分泌，因此有利于募集携带同源趋化因子（C-X-C基序）受体3（CXCR 3）的T细胞。此外，在抗IFN γ抗体治疗后，TC-1肿瘤中CXCL 9的表达显著降低，但CXCL 10的表达不显著降低。体外实验表明，IFNγ和TNFα可诱导TC-1细胞高表达CXCL 9。此外，TC-1细胞中CXCL 9的抑制降低了接种小鼠中浸润肿瘤的CD 8 + T细胞的比例，同时增加了CD 4 + T细胞的比例，从而改变了T细胞亚群分布。我们的结论是，管理L。基于单核细胞生成素的抗癌疫苗调节TH 1趋化因子应答，并且恶性细胞是这些趋化因子的重要来源。
The ability of Listeria monocytogenes-based anticancer vaccines to induce tumor regression depends on the responsiveness of malignant cells to interferon γ (IFNγ). Inhibition of IFNγ limits the recruitment of T cells to the tumors of vaccinated mice. We hypothesized that vaccination with immunotherapeutic L. monocytogenes induces the IFNγ-dependent production of chemokines that regulate the migration of tumor-infiltrating T cells. To gain further insights into this issue, we examined the chemokine responses of a transplantable, human papillomavirus (HPV)-immortalized murine tumor model (TC-1) following the administration of a L. monocytogenes-based immunotherapeutic agent that expresses E7 from HPV-16. Here, we report that the administration of L. monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X-C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3). Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was significantly reduced upon anti-IFNγ antibody treatment. CXCL9 was highly expressed by TC-1 cells following the administration of IFNγ and tumor necrosis factor α (TNFα), in vitro. Moreover, the inhibition of CXCL9 in TC-1 cells reduced the proportion of CD8+ T cells infiltrating tumors in vaccinated mice, while increasing that of CD4+ T cells, thus altering T-cell subset distribution. We conclude that the administration of L. monocytogenes-based anticancer vaccines regulates TH1 chemokine responses and that malignant cells are an important source of these chemokines.
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影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
4.3
作者：
Huang, H;Liu, YQ;Xiang, J
通讯作者：
Xiang, J
影响因子：
4.4
作者：
Peng, XH;Hussain, SF;Paterson, Y
通讯作者：
Paterson, Y
影响因子：
3.7
作者：
Groom JR;Luster AD
通讯作者：
Luster AD
影响因子：
4.4
作者：
Gorbachev, Anton V.;Kobayashi, Hirobito;Fairchild, Robert L.
通讯作者：
Fairchild, Robert L.