Decipher Tumor Microenvironment
Cancer research has long been impaired by the limitations of the use of animal models characterized by an environment highly dissimilar to the human one, frequently resulting in promising but ultimately clinically ineffective treatments. The engraftment of CD34+ haematopoietic stem cells in the triple knockout NCG mouse allows the reconstitution of a complete human immune system, with mature T cells, NK cells and macrophages. The human immune system could also be enhanced by the expression of human cytokines that will improve the immune system development. In order to recapitulate human tumor micro-environment, tumor cell lines from different tissue origins were engrafted on these advanced humanized immune system mice (HM). The obtained model allows the examination of xenograft growth in the context of a human immune system and resultant tumor microenvironment.
We describe here how we developed, validated and used a unique IMC panel to analyze the phenotype and the function of the infiltrating human immune cells, the remaining mouse immune macrophages and the developed tumor structure, at once, in HM grafted with 4 different tumor cell lines.
This analysis will allow to provide a comprehensive dataset of tumor mouse models, in order to assess the therapeutic efficacies of immune-targeted treatments in a suitable and relevant in vivo context.
Authors:
- Ha-Yeon Kim-Pénard
- Bénédicte Buttard
- Charline Boulot
- Céline Coppard
- Kiave-Yune Ho Wang Yin
- Aïda Meghraoui-Kheddar
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