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P10. Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8+ T cell and B cell responses but improves clinical efficacy in a murine pancreatic carcinoma model

Background

Multiple studies have shown that dendritic cell (DC)-based vaccines can induce antitumor immunity. Previously, we reported that gemcitabine enhances the efficacy of DC vaccination in a mouse model of pancreatic carcinoma. The present study aimed at investigating the influence of gemcitabine on vaccine-induced anti-tumoral immune responses in a syngeneic pancreatic cancer model.

Material and methods

Subcutaneous or orthotopic pancreatic tumours were induced in C57BL/6 mice using Panc02 cells expressing the model antigen OVA (PancOVA). Bone marrow-derived DC were loaded with soluble OVA protein (OVA-DC). Animals received gemcitabine twice weekly. OVA-specific CD8+ T cells and antibody titers were monitored by FACS analysis and ELISA, respectively.

Results

Gemcitabine enhanced clinical efficacy of the OVA-DC vaccine. Interestingly, gemcitabine significantly suppressed the vaccine-induced frequency of antigen-specific CD8+ T cells and antibody titers. DC migration to draining lymph nodes and antigen cross-presentation were unaffected. Despite reduced numbers of tumour-reactive T cells in peripheral blood, in vivo cytotoxicity assays revealed that CTL-mediated killing was preserved. In vitro assays revealed sensitization of tumour cells to CTL-mediated lysis by gemcitabine. In addition, gemcitabine facilitated recruitment of CD8+ T cells into tumors in DC-vaccinated mice. T and B cell suppression by gemcitabine could be avoided by starting chemotherapy after two cycles of DC vaccination.

Conclusions

Gemcitabine enhances therapeutic efficacy of DC vaccination despite its negative influence on vaccine-induced T cell proliferation. Quantitative analysis of tumour-reactive T cells in peripheral blood may thus not predict vaccination success in the setting of concomitant chemotherapy.

Author information

Correspondence to C Bauer.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Gemcitabine
  • Pancreatic Carcinoma
  • Panc02 Cell
  • Dendritic Cell Vaccination
  • Dendritic Cell Migration