Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona.
Immunobiology Laboratory, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid.
Ann Oncol. 2017 Dec 1;28(suppl_12):xii44-xii55. doi: 10.1093/annonc/mdx237.
Dendritic cells (DCs) are the main professional antigen-presenting cells for induction of T-cell adaptive responses. Cancer cells express tumor antigens, including neoantigens generated by nonsynonymous mutations, but are poor for antigen presentation and for providing costimulatory signals for T-cell priming. Mounting evidence suggests that antigen transfer to DCs and their surrogate presentation on major histocompatibility complex class I and II molecules together with costimulatory signals is paramount for induction of viral and cancer immunity. Of the great diversity of DCs, BATF3/IRF8-dependent conventional DCs type 1 (cDC1) excel at cross-presentation of tumor cell-associated antigens. Location of cDC1s in the tumor correlates with improved infiltration by CD8+ T cells and tumor-specific T-cell immunity. Indeed, cDC1s are crucial for antitumor efficacy using checkpoint inhibitors and anti-CD137 agonist monoclonal antibodies in mouse models. Enhancement and exploitation of T-cell cross-priming by cDC1s offer opportunities for improved cancer immunotherapy, including in vivo targeting of tumor antigens to internalizing receptors on cDC1s and strategies to increase their numbers, activation and priming capacity within tumors and tumor-draining lymph nodes.
树突状细胞（DCs）是诱导 T 细胞适应性反应的主要专业抗原呈递细胞。癌细胞表达肿瘤抗原，包括由非同义突变产生的新抗原，但抗原呈递能力差，不能提供 T 细胞启动的共刺激信号。越来越多的证据表明，抗原向 DCs 的转移及其在主要组织相容性复合体 I 和 II 分子上的替代呈递以及共刺激信号对于诱导病毒和癌症免疫至关重要。在众多的 DCs 中，BATF3/IRF8 依赖性传统 DC 型 1（cDC1）擅长交叉呈递肿瘤细胞相关抗原。cDC1 在肿瘤中的位置与 CD8+T 细胞的浸润增加和肿瘤特异性 T 细胞免疫相关。事实上，在小鼠模型中，cDC1 对于使用检查点抑制剂和抗 CD137 激动性单克隆抗体的抗肿瘤疗效至关重要。cDC1 对 T 细胞交叉引发的增强和利用为改善癌症免疫治疗提供了机会，包括将肿瘤抗原靶向内吞受体在 cDC1 上，以及增加其数量、在肿瘤和肿瘤引流淋巴结内的激活和启动能力的策略。
