biostudies-literatureMorton JJNational Cancer Institute (NCI)Karsh Family FoundationNIDCD NIH HHSPeter and Rhonda Grant FoundationU.S. Department of Defense (DOD)NCI NIH HHSNational Institute on Deafness and Other Communication Disorders (NIDCD)Daniel and Janet Mordecai FoundationAmerican Cancer Society (ACS)Anschutz Medical Campus, University of Colorado (CU AMC)Children's Diabetes Foundation (CDF)2053-2065https://www.ebi.ac.uk/biostudies/studies/S-EPMC12641387biostudies-literatureUnknown5(11)A fundamental limitation of HLA-A matched humanized mice (mHM), generated with donor hematopoietic stem and progenitor cells and bearing patient-derived xenografts, is that the fidelity of the interaction between the immune system and implanted tumors is limited by lack of thymic T-cell education. We created a model with patient-matched thymic and tumor tissue by using patient peripheral blood mononuclear cells reprogrammed into induced pluripotent stem cells to generate stem cell-derived thymic organoids (sTOs). When implanted in thymectomized mHM, which were subsequently engrafted with patient melanoma tissue (autologous, or mHMTA), sTOs expressed thymic tissue markers EPCAM, KRT5, and KRT8 and contained developing double-positive T cells. mHMTA had more activated HLA-DR+ T cells in theiCancer research communicationsAutologous Thymic Organoids Support Functional T-cell Education and Enhance Antitumor Immunity in Humanized Mice with Melanoma Xenografts.PMC12641387P30 CA046934ACS-IRG 16-184-56P30-CA046934T32 DC012280T32DC012280R01 CA149456R01CA149456CA171179Alzofon NMorton JJRamos SABarra JMThomas CMWeaver ANMedina TMRobinson WGao DNieto CJimeno AArmitage LHKeysar SBChimed TSLe PNRuss HABaker ASMiller BfalseAutologous Thymic Organoids Support Functional T-cell Education and Enhance Antitumor Immunity in Humanized Mice with Melanoma Xenografts.A fundamental limitation of HLA-A matched humanized mice (mHM), generated with donor hematopoietic stem and progenitor cells and bearing patient-derived xenografts, is that the fidelity of the interaction between the immune system and implanted tumors is limited by lack of thymic T-cell education. We created a model with patient-matched thymic and tumor tissue by using patient peripheral blood mononuclear cells reprogrammed into induced pluripotent stem cells to generate stem cell-derived thymic organoids (sTOs). When implanted in thymectomized mHM, which were subsequently engrafted with patient melanoma tissue (autologous, or mHMTA), sTOs expressed thymic tissue markers EPCAM, KRT5, and KRT8 and contained developing double-positive T cells. mHMTA had more activated HLA-DR+ T cells in thei2025-01-01T00:00:00Z2025 Nov2026-06-05T19:36:28.047Z2026-05-21T03:10:58.573ZS-EPMC126413874112960110.1158/2767-9764.CRC-25-0357