Inadequate nature of the antitumor CTL response results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC

We have data available on the inadequate nature of the antitumor CTL response, generated in a syngeneic mouse tumor model expressing an Ag derived from the early region 1A of human adenovirus type 5.

We demonstrated using this syngeneic mouse tumor model that the inadequate nature of the antitumor CTL response is not due to direct Ag presentation by the tumor cells, but results from presentation of tumor-derived Ag by nonactivated CD11c(+) APC. Although this event results in division of naive CTL in tumor draining lymph nodes, it does not establish a productive immune response. Treatment of tumor-bearing mice with dendritic cell-stimulating agonistic anti-CD40 mAb resulted in systemic efflux of CTL with robust effector function capable to eradicate established tumors. For efficacy of anti-CD40 treatment, CD40 ligation of host APC is required because adoptive transfer of CD40-proficient tumor-specific TCR transgenic CTL into CD40-deficient tumor-bearing mice did not lead to productive antitumor immunity after CD40 triggering in vivo. CpG and detoxified LPS (MPL) acted similarly as agonistic anti-CD40 mAb with respect to CD8(+) CTL efflux and tumor eradication. Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity.

• organism type
• Mus musculus,
• unidentified adenovirus

• cell type
• cytotoxic T lymphocyte

• molecule type
• lipopolysaccharide,
• CD8,
• Major histocompatibility complex class II,
• CpG,
• T cell receptor,
• CD11c

• organ type
• human lymph node

created over 16 years ago (2 March 2009)    last modified over 12 years ago (17 September 2012)   [ RDF ]   [ RelFinder ]