B7-negative versus B7-positive P815 tumor: differential requirements for priming of an antitumor immune response in lymph nodes.
Efficient T cell activation requires two synergistic but distinct signals derived from antigenic peptides presented by the MHC and from costimulatory molecules, particularly those belonging to the B7 family. Lack of B7-CD28 interaction may cause unresponsiveness of T cells to subsequent exposure to Ag. Nevertheless, immunization by some B7- tumors induces an antitumor immune response. We found that the immune response against two B7- tumors, the mouse P815 mastocytoma and the E7C3 melanoma, requires host-derived B7, since blockage of the B7-CD28 interaction facilitates tumor growth and eliminates an antitumor response. B7 costimulation is provided in the regional, tumor-draining lymph nodes for the induction of a primary CTL response against both B7+ tumor and B7- tumor. However, the induction of a CTL response to B7+ tumors and its clonal expansion may occur at tumor sites in addition to secondary lymphoid organs so as to generate more effective tumor immunity.
Yang
G
G
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
Mizuno
M T
MT
Hellström
K E
KE
Chen
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018122:B7-1 Antigen / Q000032:analysis*; D018106:CD28 Antigens / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D005260:Female; D007114:Immunization / Q000379:methods*; D007157:Immunologic Surveillance / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019041:L-Selectin