About this Research Topic
Gaining knowledge of human physiology and pathophysiology is often hampered by restricted access to human tissues or limited to performing in-vitro assays. Furthermore, the development of novel therapeutics for cancer immunotherapy, autoimmune- and inflammatory diseases is tightly restricted by the use of human samples before moving to clinical trials, which is generally slow and costly.
Human Immune System (HIS) mice - immunodeficient mice reconstituted with a human immune system – offer the unique opportunity to comprehensively study human infectious disease, hematopoiesis, autoimmunity, and tumor immunity in vivo. Recent progress in HIS mouse models, in which recipient immunodeficient mice carry several gene mutations or express human cytokines and self-recognition molecules, have improved human hematopoietic stem and progenitor cell engraftment as well as functional immune cell development in primary and secondary lymphoid tissues. These advanced HIS models may allow us to more precisely characterize human hematopoiesis as well as the human immune response against cancer than previous in vivo models.
However, several critical issues remain in current HIS mouse models:
1) Suboptimal thymopoiesis, insufficient proper selection of human T lymphocytes, as well as limited MHC-restricted immune responses in the periphery
2) Lack of mature human B lymphocyte differentiation
3) Inefficient migration of human immune cells into secondary lymphoid and into non-lymphoid tissues (such as the intestine)
4) Poor development of human erythrocytes and platelets
5) Unclear role of human innate immune cells (such as tumor-associated macrophages and myeloid-derived suppressor cells) and their crosstalk with adaptive immune cells in the tumor microenvironment
6) Heterogeneous engraftment potential of patient-derived tumor cells
7) Lack of well-characterized human hematopoietic stem cell (HSC) niche
In addition, whilst many types of HIS mice are now available, it is unclear which specific HIS mouse model is most suitable for a specific research area/question.
The current Research Topic calls for the submission of Original Research and Review articles that focus on:
• The development and refinement of HIS mouse models, which can be used to study human hematopoiesis (both normal and malignant) as well as human immune responses to cancer
• Assessing the effects of cancer immunotherapies using HIS mouse models
• Comparing different HIS mouse models in the context of tumor development and functional immune response against cancer
• Characterization of the human HSC niche in HIS mice
Keywords: humanized mice, xenograft, human immune system, hematopoiesis, cancer immunotherapy
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