Laboratory of Lymphocyte Dynamics, Rockefeller University, New York, NY, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sci Immunol. 2024 Oct 4;9(100):eadq8843. doi: 10.1126/sciimmunol.adq8843.
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.
树突状细胞 (DCs) 具有独特的将肿瘤抗原运送到肿瘤引流淋巴结 (tdLNs) 的能力，并与肿瘤微环境 (TME) 中的效应 T 细胞相互作用，介导天然抗肿瘤免疫和检查点阻断免疫治疗的反应。使用基于 LIPSTIC（通过 SorTagging 细胞间接触标记免疫伙伴关系）的单细胞转录组学，我们鉴定出能够在 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，具有相似超激活转录表型的 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，相对较小比例的 DC 负责 tdLN 和 TME 中大多数抗原呈递给 CD4 和 CD8 肿瘤特异性 T 细胞，并且经典检查点阻断增强了两个部位 CD40 驱动的 DC 激活。
