biostudies-literatureMoquin-Beaudry GFondation Charles-BruneauFonds de Recherche du Québec - SantéCanadian Institutes of Health Research100153https://www.ebi.ac.uk/biostudies/studies/S-EPMC9017190biostudies-literatureUnknown2(1)Modeling the tumor-immune cell interactions in humanized mice is complex and limits drug development. Here, we generated easily accessible tumor models by transforming either primary skin fibroblasts or induced pluripotent stem cell-derived cell lines injected in immune-deficient mice reconstituted with human autologous immune cells. Our results showed that fibroblastic, hepatic, or neural tumors were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice. Characterization of tumor-immune infiltrates revealed high expression levels of the dysfunction markers Tim3 and PD-1 in T cells and an enrichment in regulatory T cells, suggesting rapid establishment of immunomodulatory phenotypes. Inhibition of PD-1 by Nivolumab in humanized mice resuCell reports methodsAutologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.PMC9017190MOP-102709M'Callum MADal Soglio DMaggiorani DPaganelli MHaddad ELe OLi YMoquin-Beaudry GBenabdallah BGuimond JVEllezam BRaggi CBeausejour CColas CfalseAutologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.Modeling the tumor-immune cell interactions in humanized mice is complex and limits drug development. Here, we generated easily accessible tumor models by transforming either primary skin fibroblasts or induced pluripotent stem cell-derived cell lines injected in immune-deficient mice reconstituted with human autologous immune cells. Our results showed that fibroblastic, hepatic, or neural tumors were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice. Characterization of tumor-immune infiltrates revealed high expression levels of the dysfunction markers Tim3 and PD-1 in T cells and an enrichment in regulatory T cells, suggesting rapid establishment of immunomodulatory phenotypes. Inhibition of PD-1 by Nivolumab in humanized mice resu2022-01-01T00:00:00Z2022 Jan2025-04-04T19:10:11.199Z2025-04-04T19:10:11.199ZS-EPMC90171903547487110.1016/j.crmeth.2021.100153