The ability of two Listeria monocytogenes vaccines targeting human papillomavirus-16 E7 to induce an antitumor response correlates with myeloid dendritic cell function.
Previous work from our laboratory has shown that Lm-LLO-E7 induces complete regression of approximately 75% of established TC-1 tumors, whereas Lm-E7 only slows the growth of such tumors. In this study, we examine the effects of Lm-LLO-E7 vs Lm-E7 on APCs. We hypothesize that the difference in antitumor efficacy of the two vaccines is due to the ability of each of these vectors to render immature dendritic cells (DCs) effective APCs in terms of MHC class II or costimulatory molecule expression. We also examine the ability of these vectors to stimulate cytokine production by DCs. Both vectors induced IL-12 and TNF-alpha, but only Lm-LLO-E7 induced IL-2 production by DCs. Lm-LLO-E7 also induced significantly higher levels of MHC class II molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7. Interestingly, a shift of CD11c(+) cells from CD86(low) to CD86(high) is observed post-Lm-LLO-E7 infection. A similar shift is also observed for B7-H1 and B7-DC molecules. Moreover, Lm-LLO-E7, but not Lm-E7-pulsed DCs, stimulate naive T cell proliferation. These results indicate that Lm-LLO-E7 is more effective than Lm-E7 at inducing DC maturation. This effect is independent of the E7 Ag, because Lm-LLO-NP, and a mixture of Lm-LLO-NP and Lm-E7 induce the same changes in DC phenotype as Lm-LLO-E7. Taken together, the changes in DC expression correlate well with the differences in antitumor efficacy between these two vaccines.
Peng
Xiaohui
X
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hussain
S Farzana
SF
Paterson
Yvonne
Y
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001798:Blood Proteins / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D001428:Bacterial Vaccines; D001798:Blood Proteins; D019013:CD40 Antigens; D019496:Cancer Vaccines; C498919:Cd274 protein, mouse; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009856:Oncogene Proteins, Viral; C556977:PDCD1LG2 protein, human; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein; D014758:Viral Core Proteins; C059731:oncogene protein E7, Human papillomavirus type 16