Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade
Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade
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DOI：
10.1016/j.clim.2017.09.002
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发表时间：
2017-10-01
影响因子：
8.6
通讯作者：
Steinberger, Peter
中科院分区：
文献类型：
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作者：
Grabmeier-Pfistershammer, Katharina;Stecher, Carmen;Steinberger, Peter
用来源于建立慢性感染的病毒或肿瘤抗原的抗原持续刺激导致T细胞耗尽。共抑制受体如PD-1和CTLA-4在耗尽的T细胞上起免疫检查点的作用。用抗体阻断这些分子可以提高对癌细胞的免疫力。靶向其他共抑制受体的免疫检查点抑制剂可能在改善T细胞功能方面具有类似的作用，因此也可用于癌症治疗。单独的LAG-3和CTLA-4或与PD-L1组合，靶向BTLA和TIM-3的抗体增强CD 8 T细胞增殖。此外，我们的结果表明，阻断BTLA和TIM-3与PD-1的组合可能在增强耗尽的人T细胞的应答方面特别有效。(C)2017爱思唯尔公司All rights reserved.
Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy.Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides.Antibodies targeting BTLA and TIM-3 enhanced CD8 T cell proliferation. Moreover, our results indicate that blocking BTLA and TIM-3 in combination with PD-1 might be especially effective in enhancing responses of exhausted human T cells. (C) 2017 Elsevier Inc. All rights reserved.