title: Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap.
abstract: Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in the context of a human immune system and resultant tumor microenvironment, and recent studies have highlighted the increased similarities in attendant tumor structure, metastasis, and signaling to those features in cancer patients. This setting also facilitates the examination of investigational cancer therapies, including new immunotherapies. This review discusses recent advancements in the generation and application of HM models, their promise in cancer research, and their potential in generating clinically relevant treatments. This review also focuses on current efforts to improve HM models by engineering mouse strains expressing human cytokines or HLA proteins and implanting human bone, liver, and thymus tissue to facilitate immune cell maturation and trafficking. Finally, we discuss how these improvements may help direct future HM model cancer studies. Cancer Res; 76(21); 6153-8. ©2016 AACR.
authors: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: J Jason
authors: JJ
authors: Morton
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado.
authors: Gregory
authors: G
authors: Bird
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado.|Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado School of Medicine, Aurora, Colorado.
authors: Yosef
authors: Y
authors: Refaeli
authors: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado. antonio.jimeno@ucdenver.edu.|Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado School of Medicine, Aurora, Colorado.|Department of Otolaryngology, University of Colorado School of Medicine, Aurora, Colorado.
authors: Antonio
authors: A
authors: Jimeno
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D016207:Cytokines