Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation, 1st Edition

Models in Discovery and Translation

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation, 1st Edition,Gerard Socie,Bruce R. Blazar,ISBN9780124160040

Socie   &   Blazar   

Academic Press




276 X 216

A definitive work from leading HSCT labs which coalesces the translational aspects of immunological mechanisms of GVHD and GVL

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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


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.


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

Gerard Socie

Affiliations and Expertise

Professor of Hematology, University Paris VII Head, Department of Hematology, Immunology, Oncology APHP Hospital Saint Louis Rare Aplasies Médullaires Inserm UMR France

Bruce R. Blazar

Affiliations and Expertise

Regents Professor and CCRF Chair in Pediatric Oncology Chief, Pediatric Blood and Marrow Transplantation Program Director, Clinical and Translational Science Institute Associate Vice President for Clinical and Translational Science, AHC Vice Dean for Clinical Investigation University of Minnesota School of Medicine USA

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation, 1st Edition




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




Quotes and reviews

"Socié and Blazar provide clinical and scientific researchers with 12 chapters on research on allogenic hematopoietic stem cell transplantation (HSCT) and implications for translational practice."--Reference and Research Book News, August 2013
"Bruce Blazar and Gérard Socié have put together an important book on the Immune Biology of Stem Cell Transplants. The Authors chosen for specific chapters are all recognized experts in their field. This book will be very popular among young scientists in training, as well as among experienced transplanters."--Andrea Bacigalupo, MD, Head of the Department of Hematology at Ospedale San Martino in Genoa, Italy
"Self/non-self discrimination is a fundamental requirement of life. Accordingly, vertebrates are equipped with an adaptive immune system that is eminently self-referential: it is selected on self-molecules, sustained by self-molecules, and activated in the presence of self-molecules. Therefore, what might be the consequences of introducing a mature immune system in a novel "non-self" host? The consequences are many. Some are predictable and dreadful (e.g., graft-vs.-host disease), other unexpected and awe-inspiring (e.g., the graft-vs.-leukemia effect). Nonetheless, when allogeneic hematopoietic stem cell transplantation was introduced in medicine, it would have been impossible to anticipate its profound impact on our understanding of immunobiology. Gérard Socié and Bruce Blazar have taken up the gauntlet. They have assembled a dream team of experts who present a clear, comprehensive, critical and exciting picture of the current knowledge in immunobiology of allogeneic hematopoietic stem cell transplantation."--Claude Perreault, PhD, Professor and Canada Research Chair in Immunobiology Institute for Research in Immunology and Cancer Université de Montréal

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