B. Giri1, A. Ferrantella1, P. Sharma1, V. Sethi1, S. Modi1, Z. Malchiodi1, B. Garg1, S. Ramakrishnan1, S. Lavania1, S. Banerjee1, A. Saluja1, V. Dudeja1 1University Of Miami,Surgery,Miami, FL, USA
Introduction: Dendritic cells (DCs) are an up and coming technique for immune cell vaccination in tumor control strategies. We evaluated whether absence of heat shock protein 70 in dendritic cells altered their antitumor properties.
Methods: Dendritic cells from tumor bearing mice from either WT or HSP70-/- mice were selected by pan dendritic cell isolation kit. Then they were inoculated in mice with WT or HSP70-/- background and then given a tumor challenge of pancreatic cancer with KPC cells. In another experiment, WT or HSP70-/- dendritic cells were exposed to tumor cell lysates derived from the mouse pancreatic cancer cell line, KPC, in vitro.
Results: Tumors that were formed in WT mice receiving HSP70-/- DC were smaller than those receiving WT Dendritic cells. Overall vaccination with DC decreased tumor formation rate in both WT and KO mice but the decrease in tumor size was greater when HSP70-/- DC were implanted. Similarly, HSP70-/- dendritic cells had greater expression of anti-tumorigenic MHCII peptide on their surface when they were exposed to tumor lysates from KPC cells suggesting that HSP70 deficient DCs were more adept at mounting an anti-tumor immune effect.
Conclusion: HSP70 modulates dendritic cell function in the immune response against cancer.