Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization.
There is considerable controversy as to whether necrotic (lysate) or apoptotic tumor cells serve as the superior source of multiple tumor-associated antigens (TAAs) to pulse dendritic cells (DCs) for immunotherapeutic applications. Here, we show that standard procedures to induce apoptosis by UVB irradiation unequivocally result in a mixed population of viable, apoptotic, and necrotic tumor cells, necessitating additional purification. We used highly enriched apoptotic versus lysate of B16 melanoma cells to examine whether or not there are important distinctions between these two sources of TAAs for loading of DCs. Our results demonstrate that although some differences exist between the two forms of TAAs in expression of heat shock proteins, as well as production of interleukin-12 by pulsed DCs, their respective capacities to mature DCs phenotypically, as well as to elicit both effective immune priming and antitumor therapeutic efficacy in vivo when presented by DCs, are equivalent.
Kotera
Y
Y
Department of Surgery, University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0666, USA.
Shimizu
K
K
Mulé
J J
JJ
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; C052646:sarcoma glycoprotein gp96 rejection antigens; D018664:Interleukin-12