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.

中文翻译：

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癌症免疫学和免疫疗法中的抗原交叉呈递和T细胞交叉引发

树突状细胞（DC）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，但对于抗原呈递和为T细胞启动提供共刺激信号均很差。越来越多的证据表明，抗原转移到DC以及它们在主要组织相容性复合体I和II类分子上的替代表现以及共刺激信号对于诱导病毒和癌症免疫至关重要。在DC的多样性方面，依赖BATF3 / IRF8的1型常规DC（cDC1）在与肿瘤细胞相关的抗原交叉展示方面表现出色。cDC1s在肿瘤中的位置与CD8 ⁺浸润的改善有关T细胞和肿瘤特异性T细胞免疫。实际上，在小鼠模型中使用检查点抑制剂和抗CD137激动剂单克隆抗体，cDC1对于抗肿瘤功效至关重要。cDC1对T细胞交叉启动的增强和利用为改善癌症免疫疗法提供了机会，包括体内靶向肿瘤抗原使其内在化cDC1上的受体，以及增加其在肿瘤和引流淋巴结内的数量，激活和启动能力的策略。 。