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Effective antigen cross-presentation by prostate cancer patients' dendritic cells: implications for prostate cancer immunotherapy

Prostate Cancer and Prostatic Diseases volume 7, pages 63–72 (2004)Cite this article

Abstract

Despite the potency with which dendritic cells (DCs) are able to utilize the exogenous MHC I antigen cross-presentation pathway to cross-present antigen for the activation of killer T cells in model systems, concern about defects in immune function in cancer patients has led to uncertainty regarding whether immune cells derived from patients can effectively be used to generate tumor vaccines. We have undertaken a careful analysis of the potency of using DCs obtained from prostate cancer patients to cross-present antigen derived from human prostate tumor cells for the activation of antigen-specific T cells. Such DCs can be matured ex vivo into functionally active cells and are capable of cross-presenting influenza antigen derived from internalized apoptotic prostate tumor cells. Importantly, we demonstrate effective stimulation of both CD4+ and CD8+ T cells, as evident by production of IFN-γ, and the ability of CD8+ T cells to differentiate into effector CTLs. These results, defining conditions in which prostate cancer patient DCs can efficiently utilize the cross-presentation pathway and in which apoptotic tumor can serve as a source of antigen for DCs to activate T cells, demonstrate that this system warrants clinical study as a potential immunotherapy.

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Acknowledgements

We thank members of the laboratory for helpful discussions and critical review of the manuscript, P Albert for patient referral, and the Rockefeller University Hospital staff for their expertise assisting our clinical studies. This work was supported by a Burroughs Wellcome Career Award in Biomedical Science, an NIH National Research Service Award, the National Cancer Center, and a Doris Duke Clinical Scientist Development Award (MLA), and the Howard Hughes Medical Institute, NIH RO1 CA85784 and CA093507, and a Burroughs Wellcome Fund Clinical Scientist Award in Translational Research (RBD). This research was supported in part by a General Clinical Research Center Grant (M01-RR00102) from the National Center for Research Resources at the National Institutes of Health. This manuscript is dedicated to Leslie Misrock.

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Author notes

  1. D E Orange and M Jegathesan: Both contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, and Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, USA

    D E Orange, M Jegathesan, N E Blachère, M O Frank, M L Albert & R B Darnell

  2. Department of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    R B Darnell

  3. Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    H I Scher

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  1. D E Orange
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Correspondence to R B Darnell.

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Orange, D., Jegathesan, M., Blachère, N. et al. Effective antigen cross-presentation by prostate cancer patients' dendritic cells: implications for prostate cancer immunotherapy. Prostate Cancer Prostatic Dis 7, 63–72 (2004). https://doi.org/10.1038/sj.pcan.4500694

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