Cross-dressing of CD8α+ Dendritic Cells with Antigens from Live Mouse Tumor Cells Is a Major Mechanism of Cross-priming.

Live cells are the most abundant sources of antigen in a tumor-bearing host. Here, we used live tumor cells as source of antigens to investigate the mechanism underlying their immunogenicity in murine tumor models. The live tumor cells were significantly more immunogenic than irradiated or apoptotic tumor cells. We examined the interaction of live and apoptotic tumor cells with major subsets of antigen-presenting cells, i.e., CD8α+ dendritic cells (DC), CD8α- DCs, plasmacytoid DCs, and CD169+ macrophages at skin draining lymph nodes. The CD8α+ DCs captured cell-associated antigens from both live and apoptotic tumor cells, whereas CD169+ macrophages picked up cell-associated antigens mostly from apoptotic tumor cells. Trogocytosis and cross-dressing of membrane-associated antigenic material from live tumor cells to CD8α+ DCs was the primary mechanism for cross-priming of tumor antigens upon immunization with live cells. Phagocytosis of apoptotic tumor cells was the primary mechanism for cross-priming of tumor antigens upon immunization with apoptotic or irradiated cells. These findings clarify the mechanism of cross-priming of cancer antigens by DCs, allowing for a greater understanding of antitumor immune responses. ©2020 American Association for Cancer Research.