在癌症免疫监视过程中，树突状细胞 (DC) 在协调 T 细胞针对新兴肿瘤的反应中发挥着核心作用。捕获微量抗原以及肿瘤引发的共刺激信号可以驱动 DC 的成熟。 DC 上 CD91 的表达对于新生肿瘤中 T 细胞反应的交叉启动至关重要。多个 DC 和巨噬细胞亚群表达 CD91 并与肿瘤衍生的 gp96 结合以启动抗肿瘤免疫反应，但癌症免疫监视过程中 T 细胞交叉启动所需的特定 CD91 抗原呈递细胞 (APC) 尚不清楚。在这项研究中，我们确定 1 型常规 DC (cDC1) 上的 CD91 表达对于癌症免疫监视是必需的。具体而言，发现表达 CD91 的 cDC1 从肿瘤中捕获 CD91 配体 gp96，并在迁移到淋巴结后将 gp96 分配到淋巴结驻留的 APC 中。然而，捕获肿瘤来源的gp96的cDC1仅提供早期肿瘤控制，而持续和长期的肿瘤排斥是由其他gp96交​​叉引发的DC赋予宿主的。我们进一步发现 APC 中 CD91 诱导的转录组促进 T 细胞反应的交叉启动，同时下调免疫调节途径。我们的结果表明，APC 在通过 CD91 成功消除癌细胞过程中进行了精心且同步的分工。我们预测 APC 亚群的特殊功能可用于疾病的免疫治疗。

During cancer immunosurveillance, dendritic cells (DCs) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming of T-cell responses in the context of nascent tumors. Multiple DC and macrophage subsets express CD91 and engage tumor-derived gp96 to initiate antitumor immune responses, yet the specific CD91+ antigen-presenting cells (APCs) that are required for T-cell cross-priming during cancer immunosurveillance are unknown. In this study, we determined that CD91 expression on type 1 conventional DCs (cDC1) is necessary for cancer immunosurveillance. Specifically, CD91-expressing cDC1 were found to capture the CD91 ligand gp96 from tumors and, upon migration to the lymph nodes, distribute gp96 among lymph-node resident APCs. However, cDC1 that captured tumor-derived gp96 only provided early tumor control, while sustained and long-term tumor rejection was bestowed to the host by other gp96+ cross-priming DCs. We further found that the CD91-induced transcriptome in APCs promoted cross-priming of T-cell responses while downregulating immune regulatory pathways. Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.