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T cells targeted against a single minor histocompatibility antigen can cure solid tumors

Nature Medicine volume 11, pages 1222–1229 (2005)Cite this article

Abstract

T cells responsive to minor histocompatibility (H) antigens are extremely effective in curing leukemia but it remains unknown whether they can eradicate solid tumors. We report that injection of CD8+ T cells primed against the immunodominant H7a minor H antigen can cure established melanomas in mice. Tumor rejection was initiated by preferential extravasation at the tumor site of interferon (IFN)-γ–producing H7a-specific T cells. Intratumoral release of IFN-γ had two crucial effects: inhibition of tumor angiogenesis and upregulation of major histocompatibility complex (MHC) class I expression on tumor cells. Despite ubiquitous expression of H7a, dissemination of a few H7a-specific T cells in extralymphoid organs caused neither graft-versus-host disease (GVHD) nor vitiligo because host nonhematopoietic cells were protected by their low expression of MHC class I. Our preclinical model yields unique insights into how minor H antigen–based immunotherapy could be used to treat human solid tumors.

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Figure 1: H7a-specific CD8+ T lymphocytes can cure melanoma.
Figure 2: The antitumor efficacy of adoptively transferred T cells is regulated by expression of target antigen on tumor cells.
Figure 3: Preferential T-cell accumulation in the tumor is antigen independent but degranulation is antigen dependent.
Figure 4: Characterization of TILs and tumor blood vessels.
Figure 5: TIL-derived IFN-γ upregulates MHC class I expression on tumor cells and inhibits tumor angiogenesis.
Figure 6: Killing of target cells by H7a-specific effectors is TCR dependent and correlates with MHC class I expression.

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Acknowledgements

This work was supported by Grant 014271 (to C.P.) from the National Cancer Institute of Canada. M.-C.M. is supported by a training grant from the National Cancer Institute of Canada. J.-S.D. is supported by a training grant from the Fonds de la Recherche en Santé du Québec. C.P. holds a Canada Research Chair in Immunobiology. We thank J.A. Kashul for editorial assistance.

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  1. Institute of Research in Immunology and Cancer, University of Montreal, C.P. 6128, Downtown Station, Montreal, H3C 3J7, Quebec, Canada

    Marie-Christine Meunier, Jean-Sébastien Delisle, Vincent Rineau, Chantal Baron & Claude Perreault

  2. Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, H1T 2M4, Quebec, Canada

    Marie-Christine Meunier, Jean-Sébastien Delisle, Julie Bergeron, Vincent Rineau, Chantal Baron & Claude Perreault

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Correspondence to Claude Perreault.

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Supplementary information

Supplementary Fig. 1

Experimental model. (PDF 93 kb)

Supplementary Table 1

H7a genotype of mice and tumors used in this work. (PDF 37 kb)

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Meunier, MC., Delisle, JS., Bergeron, J. et al. T cells targeted against a single minor histocompatibility antigen can cure solid tumors. Nat Med 11, 1222–1229 (2005). https://doi.org/10.1038/nm1311

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