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The allure and peril of hematopoietic stem cell transplantation: overcoming immune challenges to improve success

  • Immunology & Microbiology in Miami
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Abstract

Since its inception in the mid-twentieth century, the complication limiting the application and utility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat patients with hematopoietic cancer is the development of graft-versus-host disease (GVHD). Ironically, GVHD is induced by the cells (T lymphocytes) transplanted for the purpose of eliminating the malignancy. Damage ensuing to multiple tissues, e.g., skin, GI, liver, and others including the eye, provides the challenge of regulating systemic and organ-specific GVH responses. Because the immune system is also targeted by GVHD, this both: (a) impairs reconstitution of immunity post-transplant resulting in patient susceptibility to lethal infection and (b) markedly diminishes the individual’s capacity to generate anti-cancer immunity—the raison d’etre for undergoing allo-HSCT. We hypothesize that deleting alloreactive T cells ex vivo using a new strategy involving antigen stimulation and alkylation will prevent systemic GVHD thereby providing a platform for the generation of anti-tumor immunity. Relapse also remains the major complication following autologous HSCT (auto-HSCT). While GVHD does not complicate auto-HSCT, its absence removes significant grant anti-tumor responses (GVL) and raises the challenge of generating rapid and effective anti-tumor immunity early post-transplant prior to immune reconstitution. We hypothesize that effective vaccine usage to stimulate tumor-specific T cells followed by their amplification using targeted IL-2 can be effective in both the autologous and allogeneic HSCT setting. Lastly, our findings support the notion that the ocular compartment can be locally targeted to regulate visual complications of GVHD which may involve both alloreactive and self-reactive (i.e., autoimmune) responses.

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Acknowledgments

We thankfully acknowledge the support of the Sylvester Comprehensive Cancer Center and the Sheila and David Fuente Graduate Program in Cancer Biology. The authors also thank the Sylvester Comprehensive Cancer Center for their continuous support as well as the Flow Cytometry Facility. We also wish to gratefully acknowledge the excellent studies performed by many of our departmental colleagues as well as our collaborators, Drs. Sudipto Ganguly and Leo Luznik at Johns Hopkins University. The work was supported by Grants from the National Institutes of Health (R01CA120776 and R01AI046689) (R.B.L.).

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  1. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, 33131, USA

    Robert G. Newman, Duncan B. Ross, Henry Barreras, Eckhard R. Podack & Robert B. Levy

  2. Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, 33131, USA

    Samantha Herretes, Victor L. Perez & Robert B. Levy

  3. Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, 33131, USA

    Krishna V. Komanduri & Robert B. Levy

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  1. Robert G. Newman
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  2. Duncan B. Ross
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Correspondence to Robert B. Levy.

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Newman, R.G., Ross, D.B., Barreras, H. et al. The allure and peril of hematopoietic stem cell transplantation: overcoming immune challenges to improve success. Immunol Res 57, 125–139 (2013). https://doi.org/10.1007/s12026-013-8450-7

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  • DOI: https://doi.org/10.1007/s12026-013-8450-7

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