Tumor antigen cross-presentation by tumor dendritic cells is blocked at a post-processing stage but can be reversed by selected pro-apoptotic agents (88.23)

Abstract

Abstract Cross presentation defines the unique capacity of an antigen presenting cell (APC) to present exogenous antigen via MHC class I molecules to CD8+ T cells. This process serves a critical role in host anti-tumor immunity. Dendritic cells (DC), specifically the CD8α+ subset, are specialised cross-presenting cells; however there is little understanding of how different DC subsets contribute to anti-tumour immunity. In this study we have examined the cross-presentation of a marker tumour antigen (transfected HA) expressed by the murine AB1-HA cell line. We have found that tumor antigen is constitutively cross-presented in the draining lymph node throughout disease progression and that both CD8α+ and CD8α - DC subsets are responsible for the observed cross-presentation of HA antigen to CD8+ T cells. Interestingly, tumor-infiltrating DCs fail to cross present, though they are not deficient in tumor antigen uptake or processing. Importantly, a tumor apoptosis-inducing false nucleotide agent, gemcitabine, which primes for anti-tumor immunity, also reverses the defect in antigen cross presentation of tumor DCs. These data suggest that lymph node resident CD8α+ DC are not the sole DC subset capable of cross-priming against tumor antigens and that local cross-presentation within tumors ie. TCR restimulation of tumor-infiltrating CD8 T-cells may be essential for effective anti-tumor immunity. These data have important implications for tumor immunotherapy particularly the use of immunotherapy in conjunction with tumor apoptosis-inducing therapy.