接近依赖性标记标识了驱动肿瘤特异性CD4+ T细胞反应的树突状细胞
Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4+ T cell response
影响因子:16.30000
分区:医学1区 Top / 免疫学1区
发表日期:2024 Oct 04
作者:
Aleksey Chudnovskiy, Tiago B R Castro, Sandra Nakandakari-Higa, Ang Cui, Chia-Hao Lin, Moshe Sade-Feldman, Brooke K Phillips, Juhee Pae, Luka Mesin, Juliana Bortolatto, Lawrence D Schweitzer, Giulia Pasqual, Li-Fan Lu, Nir Hacohen, Gabriel D Victora
摘要
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淋巴结（TDLN）中，并与肿瘤微环境（TME）本身中的效应T细胞相互作用，介导天然抗肿瘤的免疫和对检查点阻断免疫治疗的反应。使用肥大（通过排序细胞间触点来标记免疫伙伴关系）的单细胞转录组学，我们确定了能够在TDLN和TME中向CD4+ T细胞呈现抗原的单个DC。我们的发现表明，具有相似多活化转录表型的DC与肿瘤和TDLN中的辅助T细胞相互作用，并且检查点阻断药物会增强这些相互作用。这些发现表明，DC的一部分相对较小，负责TDLN和TME中对CD4+和CD8+肿瘤特异性T细胞的大多数抗原表现，并且经典的检查点阻断可增强CD40驱动的DC在两个地点的激活。
Abstract
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.