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A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses

Nature Medicine volume 11, pages 1244–1249 (2005)Cite this article

Abstract

Graft-versus-leukemia (GVL) response after allogeneic bone marrow transplantation (BMT) represents one of the most potent forms of immunotherapy against malignant diseases1. Antigen-presenting cells (APCs) are crucial for the induction of graft-versus-host disease (GVHD)2,3,4,5,6, the most serious complication of allogeneic BMT, but their role in GVL responses is unclear. Using a series of clinically relevant mouse GVL tumor models, we found that APCs and alloantigen expression on tumors are crucial for GVL. Moreover, APCs of host origin predominated in GVL responses although donor APCs contributed as the acuity of tumor burden decreased.

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Figure 1: APCs are required for GVL.
Figure 2: GVL responses require alloantigen expression.
Figure 3: Host APCs mediate a more robust GVL responses than donor APCs.

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Acknowledgements

This work was supported by US National Institutes of Health grants K08 AI052863-01 (to P.R.), PO1 CA 49542 (to J.L.M.F.) and R01 HL55593 (to R.K). P.R. is the recipient of the Alaina J. Enlow Scholar Award from Amy Strelzer Manasevit – National Marrow Donor Program and the New Investigator Award from American Society of Blood and Marrow Transplantation. J.L.M.F. is a recipient of the Doris Duke Distinguished Clinical Scientist Award.

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Author notes

  1. Pavan Reddy and Yoshinobu Maeda: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan Cancer Center, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109-0942, USA

    Pavan Reddy, Yoshinobu Maeda, Oleg I Krijanovski & James L M Ferrara

  2. Department of Pathology, University of Florida College of Medicine, P.O. Box 100275, Gainesville, 32610-0275, Florida, USA

    Chen Liu

  3. The Cancer Center, Hackensack University Medical Center, Hackensack University Medical Plaza, 30 Prospect Avenue/Jurist Research Building, Hackensack, 07601, New Jersey, USA

    Robert Korngold

  4. Department of Pediatrics, University of Michigan Cancer Center, 1500 East Medical Center Drive, Ann Arbor, 48109-0942, Michigan, USA

    James L M Ferrara

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  1. Pavan Reddy
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Correspondence to Pavan Reddy.

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Supplementary information

Supplementary Fig. 1

Impaired allostimulatory activity of MMB3.19 cells in an MLR. (PDF 30 kb)

Supplementary Fig. 2

Depletion of CD4+CD25+ regulatory T cells from the donor T cells prior to priming by host APCs does not alter the GVL effect. (PDF 34 kb)

Supplementary Data (PDF 23 kb)

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Reddy, P., Maeda, Y., Liu, C. et al. A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses. Nat Med 11, 1244–1249 (2005). https://doi.org/10.1038/nm1309

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