Abstract
Since their appearance, humanized mice carrying human immune system seemed promising tools to study the crosstalk between cancer and immunity. The NOD-scidIL2Rgammanull (NSG) mice engrafted with human cord blood (hCB)-CD34+ cells have been proposed to be a valuable tool to reproduce human immune system in mouse. However, the lack of solid evidences on the functionality of their human immune components limits their usage in immune-oncology. We report that (hCB)-CD34+ cells lose their ability to propagate and originate bone marrow-derived human immune cells after two serial transplantations in NSG mice. We demonstrate that transplants of bone marrow patient-derived acute myeloid leukemias (hAMLs) grow very similarly in the humanized (hCB)-CD34+ NSG and parental NSG mice. The similar extent of engraftment and development of leukemias in (hCB)-CD34+ NSG and controls suggests a poor human immune response against not compatible hAMLs. Our findings suggest that (hCB)-CD34+ NSG mice are transient and/or incomplete carriers of the human immune system and, therefore, represent a suboptimal tool to study the interaction between tumor and immune cells.
Highlights
In vitro studies are excellent tools to investigate pathways and interactions among few cellular and molecular components, they do not allow to fully recapitulate complex biological mechanisms that require several cellular and molecular players
We demonstrate that transplants of bone marrow patient-derived acute myeloid leukemias grow very in the humanized-CD34+ NSG and parental NSG mice
Our findings suggest that-CD34+ NSG mice are transient and/or incomplete carriers of the human immune system and, represent a suboptimal tool to study the interaction between tumor and immune cells
Summary
In vitro studies are excellent tools to investigate pathways and interactions among few cellular and molecular components, they do not allow to fully recapitulate complex biological mechanisms that require several cellular and molecular players. For this reason, they are incomplete models to explore the role of the immune system in many complex physiological and pathological conditions. In order to model the interactions between the human immune system and the human tumoral components, it is necessary to reproduce both in an in vivo context. Human xenografted tumors are well established in vivo model systems, where human cancer cells or tumor biopsies are heterotransplanted into immunodeficient rodents.
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