Das Mohapatra et al. observed that orders of magnitude fewer live, versus irradiated, tumor cells could immunize mice against secondary challenge in multiple models. Compared to irradiated cells, live tumor cells more strongly stimulated CD8+ T cells in vitro, and were taken up by CD8α+ DCs but not CD169+ macrophages in vivo. Antigen transfer from live cells occurred primarily via trogocytosis: DCs specifically sampled membrane elements and displayed tumor cell-derived MHC-peptide complexes, dependent on direct cell contact rather than secreted factors or exosomes. Mice lacking CD8α+ DCs failed to suppress secondary tumor challenge.
Contributed by Alex Najibi
ABSTRACT: 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 (APCs) i.e. CD8α+ DCs, CD8α- DCs, plasmacytoid DCs (pDCs) and CD169+ macrophages at skin draining lymph nodes (sdLNs). The CD8α+DCs captured cell associated antigens similarly 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 on to CD8α+ dendritic cells 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 dendritic cells, allowing for a greater understanding of antitumor immune responses.
Author Info: (1) Pathology, Brown University. (2) Immunology, University of Connecticut Health Ctr. (3) Immunology, University of Connecticut Health Ctr. (4) Immunology, University of Connectic
Author Info: (1) Pathology, Brown University. (2) Immunology, University of Connecticut Health Ctr. (3) Immunology, University of Connecticut Health Ctr. (4) Immunology, University of Connecticut Health Ctr. (5) Microbiology, New York University Langone Medical Center. (6) Immunology, University of Connecticut Health Ctr. Srivastava@uchc.edu.
