Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through their capacity to produce type III interferon (IFN-λ). By analyzing a large cohort of breast primary tumors and public transcriptomic datasets, we observed specific production of IFN-λ1 by cDC1. In addition, both IFN-λ1 and its receptor were associated with favorable patient outcomes. We show that IFN-III promotes a TH1 microenvironment through increased production of IL-12p70, IFN-γ, and cytotoxic lymphocyte-recruiting chemokines. Last, we showed that engagement of TLR3 is a therapeutic strategy to induce IFN-III production by tumor-associated cDC1. These data provide insight into potential IFN- or cDC1-targeting antitumor therapies.

中文翻译：

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IFN-III由cDC1选择性产生，并预测乳腺癌的良好临床预后。

树突状细胞在协调抗肿瘤免疫反应中起关键作用。已显示cDC1（常规树突状细胞1）子集对于抗肿瘤应答和免疫疗法应答至关重要，但在人类中的确切作用尚待进一步研究。使用多学科方法，我们证明了人类cDC1通过其产生III型干扰素（IFN-λ）的能力在抗肿瘤免疫应答中发挥重要作用。通过分析大量的乳腺癌原发肿瘤和公共转录组数据，我们观察到了cDC1特异性产生IFN-λ1。此外，IFN-λ1及其受体均与患者良好的预后相关。我们显示，IFN-III通过增加IL-12p70，IFN-γ和细胞毒性淋巴细胞募集趋化因子的产生来促进TH1微环境。持续，我们表明，TLR3的参与是一种诱导肿瘤相关性cDC1诱导IFN-III产生的治疗策略。这些数据提供了潜在的靶向IFN-或cDC1的抗肿瘤治疗的见解。