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Analyses of anti-tumor immune responses in the sentinel lymph nodes from the patients with oral

口腔癌患者前哨淋巴结抗肿瘤免疫反应分析

基本信息

批准号：
13470428
负责人：
TAKAHASHI Yuzo
金额：
$ 9.15万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470428/
关键词：
Antitumor immunity Dendritic cell Sentinel lymph nodes Costimulatory molecule 口腔癌腫瘍免疫

项目摘要

B7-H1 is one of ligands for an immunoregulatory molecule, PD-1. Our studies using a murine oral squamous cell carcinoma cell line, NRS1 revealed that the endogenously induced B7-H1 on NRS1 cells regulated negatively anti-tumor immune responses through PD-1. In contrast, the B7-H1. expressed at H1gh levels by gene transduction enhanced the antitumor responses in a PD-1-independent manner. These results suggest that B7-H1-mediated immune regulation seems to be very complicated.On one hand, B7-H1 is also induced on dendritic cells (DC) with B7-DC, wH1ch is another ligand for PD-1. Unlike B7-H1, B7-DC is selectively induced on DC. In the draining lymph nodes after the hapten sensitization, CD86^<high> DC co-expressed B7-DC witH1n the migrating CD11b^+CD11c^+ DC from the skin. The semi-mature DC, wH1ch expressed low levels of CD86 expressed B7-H1 but not B7-DC. The administration of anti-B7-H1 or anti-PD-1 monoclonal antibody at the hapten-sensitization enhanced the responses to the hapten-challenge. These results suggest that the PD-1:B7-H1 pathway is involved in tolerance induction.The inoculation of H1ghly metastatic NRS1 cells into the tongue induced a rapid expansion of CD11b^<++> large cells in the draining LN. These cells expressed low CD86 and B7-H1 and seem to induce tolerance in the sentinel LN. Our results suggest the possibility that the migrated DC in the sentinel LN caused tolerance induction, wH1ch is dependent upon B7-H1.

B7-H1是免疫调节分子PD-1的配体之一。我们使用小鼠口腔鳞状细胞癌细胞系NRS 1的研究表明，NRS 1细胞上内源性诱导的B7-H1通过PD-1负性调节抗肿瘤免疫应答。相比之下，B7-H1。通过基因转导以H1 gh水平表达的H1 gh以PD-1非依赖性方式增强抗肿瘤反应。这些结果表明，B7-H1介导的免疫调节似乎是非常复杂的，一方面，B7-DC也能诱导B7-H1在DC上表达，而B7-H1 ch是PD-1的另一个配体。与B7-H1不同，B7-DC选择性地在DC上诱导。在半抗原致敏后的引流淋巴结中，CD 86 ^<high>DC与来自皮肤的迁移性CD 11 b ^+ CD 11 c ^+ DC共表达B7-DC。半成熟DC wH 1ch表达低水平的CD 86，表达B7-H1，但不表达B7-DC。在半抗原致敏时给予抗B7-H1或抗PD-1单克隆抗体可增强对半抗原激发的应答。这些结果表明PD-1：B7-H1通路参与了免疫耐受的诱导。将H1高度转移的NRS 1细胞接种到舌中诱导了引流LN中CD 11b ^<++>大细胞的快速扩增。这些细胞表达低的CD 86和B7-H1，似乎诱导哨兵LN的耐受。我们的研究结果表明，前哨淋巴结中迁移的DC引起耐受诱导的可能性，whH 1ch依赖于B7-H1。