Aged mice develop protective antitumor immune responses with appropriate costimulation.
There is a clear decrease in CD8(+) T cell effector function with aging, a loss once thought to be intrinsic to the CD8(+) T cells. Recent studies suggest, however, that this decline may be a consequence of altered stimulatory signals within the aged lymphoid microenvironment. In this study, we compared the immune responses of young and old mice against the BM-185 pre-B cell lymphoma expressing enhanced GFP (EGFP) as a surrogate tumor Ag. Young animals develop protective immune responses when immunized with BM-185-EGFP, but aged mice do not and ultimately succumb to the tumor. However, expression of CD80 (B7.1) on the BM-185-EGFP (BM-185-EGFP-CD80) results in rejection of the tumor by both young and old animals. Additionally, injection of BM-185-EGFP-CD80 cells in young mice promotes the development of long-lasting memory responses capable of rejecting BM-185 wild-type tumors. Aged animals similarly injected did not develop antitumor memory responses. Interestingly, old animals immunized with the BM-185-EGFP-CD80 cells plus injections of the agonist anti-OX40 mAb did develop long-lasting memory responses capable of rejecting the BM-185 wild-type tumors with the same vigor as the young animals. We show that old mice have the capacity to develop strong antitumor responses and protective memory responses as long as they are provided with efficient costimulation. These results have important implications for the development of vaccination strategies in the elderly, indicating that the aged T cell repertoire can be exploited for the induction of tumor immunity.
Lustgarten
Joseph
J
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. jlustgarten@skcc.org
Dominguez
Ana Lucia
AL
Thoman
Marilyn
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000096:biosynthesis / Q000502:physiology; D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018122:B7-1 Antigen / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D045744:Cell Line, Tumor; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology; D049452:Green Fluorescent Proteins; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory; D007279:Injections, Subcutaneous; D008164:Luminescent Proteins / Q000008:administration & dosage / Q000276:immunology; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D008164:Luminescent Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; D049452:Green Fluorescent Proteins