Decreased generation of anti-tumor immunity after intrasplenic immunization

The localization of antigen and the nature of the host antigen-presenting c ells (APC) that present it to T cells are two major determinants of antigen immunogenicity, While lymph nodes appear to be the major site for T cell p riming, recently the spleen was shown to provide an optimal microenvironmen t for direct CD8(+) cytotoxic T cell (CTL) priming by tumor cells even in t he absence of known costimulatory molecules on tumor cells. We analyzed whe ther the splenic microenvironment would support T cell priming also when ho st APC are involved (cross-priming) which is probably the major pathway dur ing the generation of anti-tumor immunity. We performed immunization/challe nge experiments using different tumor cells (B7.1(+), B7.1(-) and/or beta - gal(+), beta -gal(-)) known to induce CTL to a variable extent either exclu sively by cross-priming (B7(-)) or at least partially by direct priming (B7 (-)). Our results demonstrate that tumor take in the spleen required much l ess cells than at a subcutaneous injection site. Additionally, intrasplenic immunization was invariably ineffective compared to subcutaneous immunizat ion. We further showed that B cells were not responsible for the inefficien t intrasplenic immunization. Therefore delivering the tumor cell antigens i nside the spleen by intrasplenic immunization did not improve but rather de creased the efficacy of tumor cell vaccines.