Dendritic Cells Prime Anti-Tumor CD8 <sup>+</sup> T Cell Responses Through MHC-Dressing

Abstract

Antigen cross-presentation, wherein dendritic cells (DC) present exogenous antigen on MHC-I molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8+ T cell responses. Here, we demonstrate that MHC-dressing, an antigen presentation pathway in which DCs acquire and display intact peptide:MHC-I molecules, is critical for anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8+ T cell activation in wo 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, which was not ablated upon genetic inactivation of tumor antigen cross-presentation. Transfer of human tumor-derived HLA molecules to myeloid cells was detected in vitro and in human tumor xenografts. Inconclusion, MHC-I-dressing is crucial for anti-tumor CD8+ T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation, MHC-dressing might also enable DCs to more faithfully and efficiently mirror the cancer cell peptidome.