Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8⁺ T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8⁺ T cell activation in two subcutaneous tumor models. In vivo acquisition of tumor-derived peptide:MHC-I molecules by DCs was sufficient to induce antigen-specific CD8⁺ T cell priming. Transfer of tumor-derived human leukocyte antigen (HLA) molecules to myeloid cells was detected in vitro and in human tumor xenografts. In conclusion, MHC-I cross-dressing is crucial for anti-tumor CD8⁺ T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation, MHC cross-dressing might also enable DCs to more faithfully and efficiently mirror the cancer cell peptidome.

抗原交叉呈递，其中树突状细胞 (DC) 在主要组织相容性 I 类 (MHC-I) 分子上呈递外源抗原，被认为是 DC 启动肿瘤特异性 CD8 ⁺ T 细胞应答的主要机制。在这里，我们证明MHC-I异装（一种抗原呈递途径，DC在其中获得并展示完整的肿瘤衍生肽：MHC-I分子）在协调抗肿瘤免疫中也很重要。在两个皮下肿瘤模型中，癌细胞 MHC-I 表达是最佳 CD8 ⁺ T 细胞激活所必需的。 DC体内获得肿瘤衍生肽：MHC-I 分子足以诱导抗原特异性 CD8 ⁺ T 细胞启动。在体外和人类肿瘤异种移植物中检测到肿瘤来源的人类白细胞抗原（HLA）分子向骨髓细胞的转移。总之，MHC-I 异装对于 DC 启动抗肿瘤 CD8 ⁺ T 细胞至关重要。除了定量增强肿瘤抗原呈递之外，MHC 异装还可能使 DC 能够更忠实、更有效地镜像癌细胞肽组。