In the Sp6 mouse plasmacytoma model, a whole cell vaccination with Sp6 cells expressing de novo B7-1 (Sp6/B7) induced an anatomically localized and cytotoxic T cells (CTLs)-mediated protection against wild type (WT) Sp6. Both WT Sp6 and Sp6/B7 showed a down-regulated expression of MHC H-2 Ld . Increase of H-2 Ld expression by cDNA transfection (Sp6/B7/Ld ) raised tumour immune protection and shifted most CTL responses towards H-2 Ld -restricted antigenic epitopes. The tumour-protective responses were not specific for the H-2 Ld -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 naïve mice, were detected in immunised mice as well as in splenocytes from naïve 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 receptors (TLRs) triggering induces gp70 expression. DAMPs released by CTL-mediated killing of Sp6/B7-Sp6/B7/Ld cells migrated to draining lymph nodes during immunisation may activate gp70 expression and presentation in most resident antigen presenting cells (APCs). The same could also apply for MuMLV virus particles present in Sp6-cytosol, discharged by dying cells and superinfecting APCs. The outcome of such a massive gp70 cross-presentation would likely be tolerogenic for the high affinity AH1-gp70-specific CTLs 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. This article is protected by copyright. All rights reserved.

Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of myeloma

MAZZOCCO, Marta
Investigation
;
MARTINI, Matteo
Investigation
;
STEFANI, Elisabetta
Investigation
;
MATUCCI, Andrea
Investigation
;
DE SANCTIS, FRANCESCO
Investigation
;
Ugel, Stefano
Conceptualization
;
Sandri, Sara
Investigation
;
Ferrarini, Giovanna
Investigation
;
CESTARI, Tiziana;FERRARI, Sergio;Bronte, Vincenzo;SARTORIS, Silvia
2015

Abstract

In the Sp6 mouse plasmacytoma model, a whole cell vaccination with Sp6 cells expressing de novo B7-1 (Sp6/B7) induced an anatomically localized and cytotoxic T cells (CTLs)-mediated protection against wild type (WT) Sp6. Both WT Sp6 and Sp6/B7 showed a down-regulated expression of MHC H-2 Ld . Increase of H-2 Ld expression by cDNA transfection (Sp6/B7/Ld ) raised tumour immune protection and shifted most CTL responses towards H-2 Ld -restricted antigenic epitopes. The tumour-protective responses were not specific for the H-2 Ld -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 naïve mice, were detected in immunised mice as well as in splenocytes from naïve 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 receptors (TLRs) triggering induces gp70 expression. DAMPs released by CTL-mediated killing of Sp6/B7-Sp6/B7/Ld cells migrated to draining lymph nodes during immunisation may activate gp70 expression and presentation in most resident antigen presenting cells (APCs). The same could also apply for MuMLV virus particles present in Sp6-cytosol, discharged by dying cells and superinfecting APCs. The outcome of such a massive gp70 cross-presentation would likely be tolerogenic for the high affinity AH1-gp70-specific CTLs 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. This article is protected by copyright. All rights reserved.
cancer immunoediting, cellular vaccines, myeloma
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/920383
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