Tumor microenvironment composition is shaped by tumor cell line-derived xenograft subtype and tumor burden in BRGSF-HIS mice

Background

The relevance of preclinical models has vastly improved with mice bearing a human immune system, especially in the context of immunotherapy. BRGSF (BALB/c Rag2^-/-, IL2R^-/-, SIRP^NOD and Flt3^-/-) is a highly immunodeficient mouse featuring reduced murine myeloid cells. BRGSF mice reconstituted with human cord blood CD34⁺ cells (BRGSF-HIS) develop functional lymphoid and myeloid compartments. This engraftment is stable over a year and mice do not develop GvHD. Additionally, myeloid compartment can be transiently boosted with exogenous human Flt3L injections. In contrary to other models which overexpress human cytokines to develop human myeloid cells, Flt3L-treated BRGSF-HIS mice do not show side effects. BRGSF-HIS mice are permissive to mouse and human cancer cell lines engraftment.

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