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Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation
Models in Discovery and Translation
- 1st Edition - December 6, 2012
- Editors: Gerard Socie, Bruce R. Blazar
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 4 1 6 0 0 4 - 0
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 9 1 4 6 5 - 1
Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation provides clinical and scientific researchers with a deep understanding of the current research in this fiel… Read more
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Request a sales quoteImmune 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.
- 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
Contributors
Foreword
Abbreviations
CH 1. Overview of the immune biology of allogeneic hematopoietic stem cell transplantation
Introduction
Immune rejection
Immune deficiency
GVHD pathophysiology
The graft-versus-leukemia effect
References
CH 2. The HLA system in hematopoietic stem cell transplantation
Introduction
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
Conclusions
Acknowledgments
References
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
References
CH 4. In vivo imaging of graft-versus-host disease and graft-versus-leukemia
Introduction
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
Conclusion
References
CH 5. Immune rejection: the immune biology of allogeneic hematopoietic stem cell transplantation (from mice to humans)
Introduction
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
References
CH 6. Strategies to improve post-transplant immunity
Introduction
Post-transplant immune deficiency
GVHD of the thymus
Interleukin-7
Keratinocyte growth factor
Sex steroid ablation
Growth hormone
T-cell precursors
Interleukin-22
Flt3L
Other cytokines and growth factors
Conclusions
References
CH 7. Tumor-associated antigens
Introduction
Biology of tumor-associated antigens
Aberrantly expressed self-antigens
Tumor-specific antigens
Mutated self-antigens
Cellular approaches to targeting TAA
Unanswered questions
Conclusion
References
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
References
CH 9. Antigen presentation and antigen-presenting cells in graft-versus-host disease
Introduction
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
References
CH 10. T-cell costimulation in graft-versus-host disease and graft-versus-leukemia effect
Introduction
B7/CD28 superfamily
TNF/TNFR superfamily
Regulation of GVHD by costimulation through tregs
Conclusions
References
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
References
CH 12. Natural CD4+CD25+FOXP3+ regulatory T cells in graft-versus-host disease
Introduction
Treg biology
Treg in experimental SCT
Treg in clinical SCT
Summary
References
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
Summary
Unanswered questions
Acknowledgments
References
CH 14. B and T cells in chronic graft-versus-host disease and graft-versus-leukemia
Introduction
Chronic graft-versus-host disease
Graft-versus-leukemia and graft-versus-tumor effects of allogeneic transplantation
From pathogenesis to therapy: cGVHD and GVL/GVT
Conclusions
References
CH 15. Natural killer cells in graft-versus-host disease and graft-versus-leukemia
Introduction
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
References
CH 16. Cytokines in graft-versus-host disease and graft-versus-leukemia
Introduction
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
References
CH 17. Chemokines and graft-versus-host disease
Introduction
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
Conclusions
Acknowledgments
References
CH 18. Intracellular sensors of immunity and allogeneic hematopoietic stem cell transplantation
Introduction
Intracellular sensors
Metabolic sensors that regulate allogeneic HSCT
Intracellular metabolic changes secondary to immunity
References
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
Conclusions
References
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
References
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
Conclusion
References
Index
- No. of pages: 536
- Language: English
- Edition: 1
- Published: December 6, 2012
- Imprint: Academic Press
- Hardback ISBN: 9780124160040
- eBook ISBN: 9780123914651
GS
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, FranceBB
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