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Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis

Cancer Gene Therapy volume 14, pages 409–420 (2007)Cite this article

Abstract

The dual role of heat shock protein 70 (HSP70), as antigenic peptide chaperone and danger signal, makes it especially important in dendritic cell (DC)-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/HSP tumor cells expressing HSP70 on DC maturation, T-cell stimulation and vaccine efficacy. We found that DCs with phagocytosis of MCA/HSP in early phase of apoptosis expressed more pMHC I complexes, stimulated stronger cytotoxic T lymphocyte (CTL) responses (40% specific killing at an E:T cell ratio of 50) and induced immune protection in 90% of mice against MCA tumor cell challenge, compared with 25% specific CTL killing activity and 60% immune protection seen in mice immunized with DC with phagocytosis of MCA/HSP in late phase of apoptosis (P<0.05). Similar results were confirmed in another EG7 tumor model also expressing HSP70. Taken together, our data demonstrate that HSP70 on apoptotic tumor cells stimulate DC maturation, and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor-specific CTL responses and immunity than DCs with phagocytosis of apoptotic tumor cells in late phase of apoptosis. These results may have an important impact in designing DC-based antitumor vaccines.

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Acknowledgements

This study was supported by research grants (MOP 63259 and 67230) from the Canadian Institute of Health Research.

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Authors and Affiliations

  1. Department of Oncology, Research Unit, Saskatchewan Cancer Agency, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    T Chan, Z Chen, S Hao, S Xu, J Yuan & J Xiang

  2. Department of Immunology, Research Unit, Saskatchewan Cancer Agency, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    T Chan, Z Chen, S Hao, S Xu, J Yuan & J Xiang

  3. Department of Pathology, Research Unit, Saskatchewan Cancer Agency, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    A Saxena & M Qureshi

  4. Gene Therapy Branch, National Institute of Dental Research, National Institute of Health, Bethesda, MD, USA

    C Zheng

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  1. T Chan
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Correspondence to J Xiang.

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Chan, T., Chen, Z., Hao, S. et al. Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis. Cancer Gene Ther 14, 409–420 (2007). https://doi.org/10.1038/sj.cgt.7701025

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