Due to their easy availability and expansion in vitro, monocyte-derived dendritic cells (moDCs) are most frequently used for tumor vaccination. Immunoglobulin-like transcript 4 (ILT4), as inhibitory receptor, has been reported to be related to DC tolerance. However, the influence of ILT4 for DC tolerance in hepatocellular carcinoma (HCC) patients has not been illustrated. In this research, we explored the expression of ILT4 on moDCs from HCC patients and its effect on moDC function. We demonstrated that the expression of ILT4 on mature DCs (mDCs) was higher in the peripheral blood from HCC patients than in that from healthy donors. The levels of cytokines IL-1β and IL-6 secreted by mDCs from both HCC patients and healthy controls, stimulated by anti-ILT4 agonistic mAb, were decreased. In contrast, the levels of IL-10 and IL-23 were upregulated. In addition, ILT4, triggered by anti-ILT4 agonistic mAb, could reduce allogeneic T cell proliferation stimulated by the mDCs. Moreover, ILT4 triggered by anti-ILT4 agonistic mAb could also reduce the ability of the mDCs to stimulate tumor cell antigen-specific autologous CD4⁺ T cells (production of IFN-γ) and CD8⁺ T cells (production of IFN-γ and IL-2). Furthermore, ILT4 expression impaired the cytotoxicity of autologous T cells induced by the mDCs against the HCC tumor cell line SMMC-7721. Our data revealed that the high expression of ILT4 promoted the immune tolerance of DCs, resulting in an inefficiency of the T cell response, a process that is exacerbated in HCC patients.

由于它们在体外易于获得和扩增，单核细胞衍生的树突细胞 (moDC) 最常用于肿瘤疫苗接种。据报道，免疫球蛋白样转录物 4 (ILT4) 作为抑制性受体与 DC 耐受性有关。然而，尚未说明 ILT4 对肝细胞癌 (HCC) 患者 DC 耐受性的影响。在这项研究中，我们探讨了 ILT4 在 HCC 患者的 moDC 上的表达及其对 moDC 功能的影响。我们证明，在 HCC 患者的外周血中，ILT4 在成熟 DC（mDC）上的表达高于健康供者的外周血。在抗 ILT4 激动性 mAb 的刺激下，HCC 患者和健康对照的 mDC 分泌的细胞因子 IL-1β 和 IL-6 的水平降低。相比之下，IL-10 和 IL-23 的水平上调。此外，由抗 ILT4 激动剂 mAb 触发的 ILT4 可以减少由 mDC 刺激的同种异体 T 细胞增殖。此外，由抗 ILT4 激动剂 mAb 触发的 ILT4 也可以降低 mDCs 刺激肿瘤细胞抗原特异性自体 CD4 的能力⁺ T 细胞（产生 IFN-γ）和 CD8 ⁺ T 细胞（产生 IFN-γ 和 IL-2）。此外，ILT4 表达削弱了由 mDC 诱导的自体 T 细胞对 HCC 肿瘤细胞系 SMMC-7721 的细胞毒性。我们的数据显示，ILT4 的高表达促进了 DC 的免疫耐受，导致 T 细胞反应效率低下，这一过程在 HCC 患者中加剧。