title: Induction of an antitumour adaptive immune response elicited by tumour cells expressing de novo B7-1 mainly depends on the anatomical site of their delivery: the dose applied regulates the expansion of the response.
abstract: De novo expression of costimulatory molecules in tumours generally increases their immunogenicity, but does not always induce a protective response against the parental tumour. This issue was addressed in the mouse Sp6 hybridoma model, comparing different immunization routes (subcutaneous, intraperitoneal and intravenous) and doses (0.5 x 10(6) and 5 x 10(6) cells) of Sp6 cells expressing de novo B7-1 (Sp6/B7). The results can be summarized as follows. First, de novo expression of B7-1 rendered Sp6 immunogenic, as it significantly reduced the tumour incidence to < or =15% with all delivery routes and doses tested, whereas wild-type Sp6 was invariably tumorigenic (100% tumour incidence). Second, long-lasting protection against wild-type Sp6 was mainly achieved when immunization with Sp6/B7 was subcutaneous: a dose of 0.5 x 10(6) Sp6/B7 cells elicited protection that was confined to sites in the same anatomical quarter as the immunizing injection. Repeated injections of the same dose extended protection against wild-type Sp6 to other anatomical districts, as well as a single injection of a 10-fold higher dose (5 x 10(6) cells). Finally, Sp6-specific cytotoxic T-lymphocyte activity was detected in draining lymph nodes, and the splenic expansion of Sp6-specific cytotoxic T-lymphocyte precursors quantitatively correlated with the dose of antigen. We conclude that activation of a protective immune response against Sp6 depends on the local environment where the immunogenic form of the 'whole tumour cell antigen' is delivered. The antigen dose regulates the anatomical extent of the protective response.
authors: Dipartimento di Patologia, Sezione di Immunologia, Università di Verona, Verona, Italy. silvia.sartoris@univr.it
authors: Silvia
authors: S
authors: Sartoris
authors: Maria G
authors: MG
authors: Testi
authors: Elisabetta
authors: E
authors: Stefani
authors: Roberto
authors: R
authors: Chignola
authors: Chiara
authors: C
authors: Guerriero
authors: Andrea
authors: A
authors: Matucci
authors: Tiziana
authors: T
authors: Cestari
authors: Aldo
authors: A
authors: Scarpa
authors: Anna P
authors: AP
authors: Riviera
authors: Giovanna
authors: G
authors: Zanoni
authors: Giuseppe
authors: G
authors: Tridente
authors: Giancarlo
authors: G
authors: Andrighetto
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry / Q000379:methods; D006825:Hybridomas / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D018122:B7-1 Antigen