Autologous Thymic Organoids Support Functional T-cell Education and Enhance Antitumor Immunity in Humanized Mice with Melanoma Xenografts.

ABSTRACT: 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 thei

SUBMITTER: Morton JJ 

PROVIDER: S-EPMC12641387 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature