title: Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of myeloma.
abstract: In the Sp6 mouse plasmacytoma model, a whole-cell vaccination with Sp6 cells expressing de novo B7-1 (Sp6/B7) induced anatomically localized and cytotoxic T cell (CTL)-mediated protection against wild-type (WT) Sp6. Both WT Sp6 and Sp6/B7 showed down-regulated expression of MHC H-2 L(d). Increase of H-2 L(d) expression by cDNA transfection (Sp6/B7/L(d)) raised tumour immune protection and shifted most CTL responses towards H-2 L(d)-restricted antigenic epitopes. The tumour-protective responses were not specific for the H-2 L(d)-restricted immunodominant AH1 epitope of the gp70 common mouse tumour antigen, although WT Sp6 and transfectants were able to present it to specific T cells in vitro. Gp70 transcripts, absent in secondary lymphoid organs of naive mice, were detected in immunized mice as well as in splenocytes from naive mice incubated in vitro with supernatants of CTL-lysed Sp6 cell cultures, containing damage-associated molecular patterns (DAMPs). It has been shown that Toll-like receptor triggering induces gp70 expression. Damage-associated molecular patterns are released by CTL-mediated killing of Sp6/B7-Sp6/B7/L(d) cells migrated to draining lymph nodes during immunization and may activate gp70 expression and presentation in most resident antigen-presenting cells. The same could also apply for Mus musculus endogenous ecotropic murine leukaemia virus 1 particles present in Sp6-cytosol, discharged by dying cells and superinfecting antigen-presenting cells. The outcome of such a massive gp70 cross-presentation would probably be tolerogenic for the high-affinity AH1-gp70-specific CTL clones. In this scenario, autologous whole-tumour-cell vaccines rescue tumour-specific immunoprotection by amplification of subdominant tumour antigen responses when those against the immune dominant antigens are lost.
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Mazzocco
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Martini
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.|Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Stefani
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matucci
authors.affiliation: Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dalla Santa
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Sanctis
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ugel
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sandri
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ferrarini
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cestari
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.|Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sartoris
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D024243:HMGB1 Protein / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006183:H-2 Antigens; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse
keywords: cancer immunoediting; cellular vaccines; myeloma