Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation

Models in Discovery and Translation

1st Edition - December 6, 2012

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  • Editors: Gerard Socie, Bruce R. Blazar
  • eBook ISBN: 9780123914651
  • Hardcover ISBN: 9780124160040

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Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation provides clinical and scientific researchers with a deep understanding of the current research in this field and the implications for translational practice. By providing an overview of the immune biology of HSCT, an explanation of immune rejection, and detail on antigens and their role in HSCT success, this book embraces biologists and clinicians who need a broad view of the deeply complex processes involved. It then moves on to discuss the immunobiology mechanisms that influence graft-versus-host disease (GVHD), graft-versus-leukemia (GVL) effect, and transplantation success. Using illustrative figures, highlighting key issues, describing recent successes and discussing unanswered questions, this book sums up the current state of HSCT to enhance the prospects for the future. Allogeneic HSCT is a medical procedure in which a patient receives blood-forming stem cells from a genetically similar but not identical donor. This procedure is commonly performed for people with diseases of the blood, bone marrow, or certain cancers, but it remains risky with many possible complications. As such, experimental practice is reserved for preclinical animal models including the mouse and dog. These animal models have been essential in developing transplant protocols, including preclinical testing of conditioning regimens, treatment of GVHD, and understanding the pathology of GVHD as well as the immunological mechanisms of GVHD and GVL effect. However, recent research has revealed significant species differences between humans and animal models that must be considered when relating animal model studies to clinical allogeneic HSCT scenarios.

Key Features

  • Brings together perspectives leading laboratories and clinical research groups to highlight advances from bench to the bedside
  • Guides readers through the caveats that must be considered when drawing conclusions from studies with animal models before correlating to clinical allogeneic HSCT scenarios
  • Categorizes the published advances in various aspects of immune biology of allegeneic HSCT to illustrate opportunities for clinical applications


Stem cell biologists, cancer biologists, immunologists, hematologists, cardiologists, oncologists, pathologist

Table of Contents

  • Contributors



    CH 1. Overview of the immune biology of allogeneic hematopoietic stem cell transplantation


    Immune rejection

    Immune deficiency

    GVHD pathophysiology

    The graft-versus-leukemia effect


    CH 2. The HLA system in hematopoietic stem cell transplantation


    Classical HLA

    The role of classical HLA in unrelated donor hematopoietic cell transplantation

    The clinical significance of non-classical HLA genes: HLA-E, (HLA-F), HLA-G and MIC genes




    CH 3. The impact of minor histocompatibility antigens in allogeneic stem cell transplantation

    From immunobiology to the impact of mHags in GVHD and GVT

    Murine mHags, challenges for the human system

    Immunobiology and biochemical identity of mHags

    Mechanisms of generation of mHags

    The impact of individual mHags on GVHD and GVT

    To match or to mismatch: paradigm shifts in the mHag field

    Hematopoietic mHags: ideal targets for separating GVT from GVHD

    Immunotherapeutic targeting of hematopoietic mHags

    Toward a broad and more effective application of mHag therapy

    Controlling naturally existing and mHag-specific CD8+ regulatory T cells

    Concluding remarks


    CH 4. In vivo imaging of graft-versus-host disease and graft-versus-leukemia


    Bioluminescence imaging

    In vivo fluorescence imaging

    Nuclear imaging (PET/SPECT)

    Magnetic resonance imaging

    Multimodal imaging of GVHD and anti-tumor responses

    Advances in imaging technology



    CH 5. Immune rejection: the immune biology of allogeneic hematopoietic stem cell transplantation (from mice to humans)


    Hematopoietic space and microenvironment

    Effector mechanisms of graft rejection

    Impact of pretransplant conditioning on effector mechanisms of rejection

    Impact of MHC-matching on risk of rejection – from mice to humans

    Impact of donor cells on risk of rejection – from mice to humans

    Impact of post-transplant immunosuppression on risk of rejection

    Future directions


    CH 6. Strategies to improve post-transplant immunity


    Post-transplant immune deficiency

    GVHD of the thymus


    Keratinocyte growth factor

    Sex steroid ablation

    Growth hormone

    T-cell precursors



    Other cytokines and growth factors



    CH 7. Tumor-associated antigens


    Biology of tumor-associated antigens

    Aberrantly expressed self-antigens

    Tumor-specific antigens

    Mutated self-antigens

    Cellular approaches to targeting TAA

    Unanswered questions



    CH 8. Impact of the conditioning regimen

    First evidence for a role of conditioning in pathophysiology of GVHD

    Mechanisms of increased GVHD

    Role of inflammation and damage to immunological organs

    Controversies and alternative explanations


    CH 9. Antigen presentation and antigen-presenting cells in graft-versus-host disease


    Major versus minor histocompatibility antigens

    Direct versus indirect presentation of miHAs and cross-priming

    The roles of host-derived hematopoietic and nonhematopoietic APCs in GVHD

    Where does T-cell priming occur?

    Priming independent of hematopoietic APCs (revisited)

    Specific hematopoietic APC subtypes in GVHD


    CH 10. T-cell costimulation in graft-versus-host disease and graft-versus-leukemia effect


    B7/CD28 superfamily

    TNF/TNFR superfamily

    Regulation of GVHD by costimulation through tregs



    CH 11. Th1/Th2 and Tc1/Tc2 cells: biology, experimental models and clinical translation

    T-helper differentiation

    Experimental transplantation models evaluating the Th1/Th2 paradigm

    Clinical transplantation and the Th1/Th2 paradigm

    Future directions/unanswered questions


    CH 12. Natural CD4+CD25+FOXP3+ regulatory T cells in graft-versus-host disease


    Treg biology

    Treg in experimental SCT

    Treg in clinical SCT



    CH 13. Role of Th17 cells and interleukin 17 in graft-versus-host disease and graft-versus-leukemia reactivity

    Discovery of Th17 cells

    Differentiation and actions of Th17 cells

    Interaction of Th17 cells with Th1, Th2, and Tregs

    Role of IL-17 and Th17 cells in preclinical models of acute graft-versus-host disease

    Role of IL-17 and Th17 cells in chronic GVHD

    Roles of cytokines that induce Th17 differentiation in GVHD

    Roles of transcription factors involved in Th17 cell differentiation in GVHD

    Role of IL-17 and Th17 cells in clinical GVHD

    Role of IL-17 and IL-23R polymorphisms in GVHD

    Roles of other Th17 cytokines in GVHD biology

    Role of IL-17 and Th17 cells in GVL reactivity


    Unanswered questions



    CH 14. B and T cells in chronic graft-versus-host disease and graft-versus-leukemia


    Chronic graft-versus-host disease

    Graft-versus-leukemia and graft-versus-tumor effects of allogeneic transplantation

    From pathogenesis to therapy: cGVHD and GVL/GVT



    CH 15. Natural killer cells in graft-versus-host disease and graft-versus-leukemia


    NK cell receptors

    NK cell signaling

    Acquisition of NK cell function

    NK cell memory

    Role of NK cells in cancer therapeutics

    Expanding NK cells

    Enhancing NK cell function to eliminate tumors

    The role of NK cells in viral therapy

    Concluding remarks


    CH 16. Cytokines in graft-versus-host disease and graft-versus-leukemia


    Stimuli for cytokine production after hematopoietic stem cell transplantation

    Acute versus chronic GVHD

    Graft-versus-leukemia effects

    Critical cytokines in GVHD pathogenesis

    Cytokines involved in Th1 differentiation

    Cytokines involved in th2 differentiation

    Cytokines involved in Th17/Treg differentiation

    Cytokines influencing myeloid development and function

    Summary and conclusions


    CH 17. Chemokines and graft-versus-host disease


    The study of GVHD: a changing paradigm

    Chemokines and the development of acute GVHD

    Chemokines and leukocyte trafficking after allogeneic HCT

    Chemokines and GVT responses

    Advances in the clinical application of chemokine biology during GVHD




    CH 18. Intracellular sensors of immunity and allogeneic hematopoietic stem cell transplantation


    Intracellular sensors

    Metabolic sensors that regulate allogeneic HSCT

    Intracellular metabolic changes secondary to immunity


    CH 19. Proteomics in graft-versus-host disease and graft-versus-leukemia

    Definition of biomarkers and pending issues for post-hematopoietic stem cell transplantation clinicians

    Current proteomics technologies for biomarker discovery

    Major phases of biomarker development

    Statistical considerations

    aGVHD biomarkers: from the identification of candidates to their validation

    Identification and validation of chronic GVHD biomarkers

    Identification of GVL and minimal residual disease (MRD) biomarkers

    Incorporating GVHD biomarkers in clinical trials

    Future research on biomarkers: from diagnosis to therapy



    CH 20. The endothelium in graft-versus-host disease and graft-versus-leukemia

    The endothelium in graft-versus-host disease

    Endothelial dysfunction caused by the conditioning regimen

    Endothelial dysfunction caused by alloreactivity of donor leukocytes

    Antigen presentation and T-cell activation by endothelial cells during GVHD

    Neovascularization during GVHD

    Inhibition of neovascularization during GVHD

    The endothelium in graft-versus-leukemia

    Conclusions and perspectives


    CH 21. Looking toward the future: an individualized approach to allogeneic transplantation

    An individualized approach to allogeneic transplantation

    The future of GVHD: diagnosis, prognosis

    The future of GVHD: treatment

    Cellular therapy

    Inhibitors of histone deacetylase

    Creating platforms for new therapies

    Prevention and treatment of relapse

    Novel immunotherapeutics

    Disease-specific conditioning regimens

    Cellular therapy for relapse: natural killer cells

    Maintenance therapy following allogeneic transplantation

    Improved anti-leukemia effects through T-cell manipulation




Product details

  • No. of pages: 536
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: December 6, 2012
  • Imprint: Academic Press
  • eBook ISBN: 9780123914651
  • Hardcover ISBN: 9780124160040

About the Editors

Gerard Socie

Dr. Gerard Socie's main field of expertise (clinical and biological); allogeneic stem cell transplantation with special focus on graft-versus-host disease and study of late effects, aplastic anemia with special focus on PNH, and Fanconi anemia. He is GCP certified (last May 2017) and the department head and head of transplantation at the Hospital Saint Louis, University of Paris VII.

Affiliations and Expertise

Professor of Hematology, University Paris VII; Head of Hematology, Immunology, Transplantation, APHP Hospital Saint Louis, Inserm UMR 1160, Paris, France

Bruce R. Blazar

Affiliations and Expertise

Regents Professor and Childrens’ Cancer Research Fund Chair in Pediatric Oncology, Department of Pediatrics, Division of Blood and Marrow Transplantation; Director, Clinical and Translational Science Institute; Vice Dean for Clinical Investigation, University of Minnesota School of Medicine, USA

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