PD-1 expression by canine T cells and functional effects of PD-1 blockade
PD-1 expression by canine T cells and functional effects of PD-1 blockade
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DOI：
10.1111/vco.12294
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发表时间：
2017-12-01
影响因子：
2.1
通讯作者：
Dow, S.
中科院分区：
文献类型：
--
作者：
Coy, J.;Caldwell, A.;Dow, S.
共抑制性检查点分子程序性死亡受体1（PD-1）可在与肿瘤细胞或巨噬细胞上表达的其配体PD-L1结合后触发T细胞功能衰竭。PD-1阻断抗体在人类癌症患者中产生了显着的效果，包括在许多晚期癌症中诱导持久的反应。因此，评估了犬PD-1特异性单克隆抗体的T细胞结合和功能活化诱导。来自健康狗的总共5-10%的CD 4 T细胞和20-25%的CD 8 T细胞表达PD-1，并且来自患有癌症的狗的T细胞上的PD-1表达上调。在功能上，PD-1抗体显著增强T细胞活化，如通过增殖和干扰素-γ（IFN-γ）产生所评估的。PD-1抗体还逆转了由犬可溶性PD-L1以及肿瘤细胞和肿瘤外植体片段诱导的T细胞抑制。这些发现表明PD-1抗体具有用于犬癌症免疫治疗的潜力。
The co-inhibitory checkpoint molecule programmed death receptor 1 (PD-1) can trigger T cell functional exhaustion upon binding to its ligand PD-L1 expressed on tumour cells or macrophages. PD-1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD-1 were assessed for T cell binding and induction of functional activation. A total of 5-10% of CD4 T cells and 20-25% of CD8 T cells from healthy dogs expressed PD-1, and PD-1 expression was upregulated on T cells from dogs with cancer. Functionally, PD-1 antibodies significantly enhanced T-cell activation, as assessed by proliferation and interferon-gamma (IFN-gamma) production. PD-1 antibodies also reversed T-cell suppression induced by canine soluble PD-L1 and by tumour cells and tumour explant fragments. These findings indicate that PD-1 antibodies have potential for use in cancer immunotherapy in dogs.