Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)–based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4 + T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4 + and CD8 + tumor–specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.

中文翻译：

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邻近依赖性标记可识别驱动肿瘤特异性 CD4 + T 细胞反应的树突状细胞


树突状细胞 （DC） 具有独特的能力，能够将肿瘤抗原转运到肿瘤引流淋巴结 （tdLN），并与肿瘤微环境 （TME） 本身的效应 T 细胞相互作用，介导天然抗肿瘤免疫和对检查点阻断免疫疗法的反应。使用基于 LIPSTIC （Labeling Immune Partnership by SorTagging Intercellular Contacts） 的单细胞转录组学，我们鉴定了能够在 tdLN 和 TME 中向 CD4 + T 细胞呈递抗原的单个 DC。我们的研究结果表明，具有相似高激活转录表型的 DC 与肿瘤和 tdLN 中的辅助性 T 细胞相互作用，并且检查点阻断药物增强了这些相互作用。这些发现表明，相对较小的 DC 是 tdLN 和 TME 中向 CD4 + 和 CD8 + 肿瘤特异性 T 细胞呈递的大部分抗原的原因，并且经典检查点阻断增强了 CD40 驱动的 DC 在这两个位点的激活。