LAUSR

Preclinical tumor oncology research relies historically on the analysis of mouse or human tumor cell lines implanted onto severely immune-deficient mouse models carrying nude, SCID or Rag mutations on different genetical background (C57Bl/6N, BalbC, NMRI, CB17 or NOD). These lines harbor defects in several leukocyte lineages among which Tc, Bc and NKc might be affected. Humanized mice are emerging models that have been transplanted with human cells or tissues (and/or equipped with human transgenes). Currently, the most advanced strains are the nonobese diabetic, severe combined immunodeficiency (NOD-SCID) mouse with complete disruptions in the interleukin-2 (IL-2) common γ-chain (IL2R γ null) receptor (NSG) and BALB/c Rag2−/− IL2R γ null SirpaNOD mice (BRGS).1 Juvenile chimera NSG or BRGS are reconstituted with hematopoietic progenitor cell (HPCs) from human cord blood yielding robust engraftment of a human immune system (HIS).. Recent work showing the binding of human IgG4 to mouse FcgR receptor reducing clinical efficacy of therapeutic antibodies highlights the need to characterize extensively the residual immune system present in these models prior humanization in order to precisely evaluate immunotherapies. In other to fulfill this task, we genetically modified the mouse genome introducing mutations involved in Tc, Bc and NKc development. We then immuno-phenotyped over 20 lines of mouse mutants produced from the same animal house to minimize the impact of microbiota on innate immune cell populations. High content cytometry analysis of BM, spleen, thymus and peripheral blood was performed in a standardized manner. The resource obtained of these immunotypes was used to highlight similarities and differences among these lines across several genetical background. This work has shown instrumental in selecting the most appropriate model to use for humanization followed before tumor implantation. Citation Format: Hervé Luche, Lillia Hadjem, Marielle Mello, Priscilla Canavese, Fabien Angelis, Anais Joachim, Sylvie Bouilly, Frederic Guinut, Frederic Fiore, Bernard Malissen, Ana Zarubica, Erwan Corcuff. Systematic immune-profiling of immune-deficient mouse models: A rational to select ideal host for tumor implantation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5190.