biostudies-literatureLi ZThe National Natural Science Foundation of China164https://www.ebi.ac.uk/biostudies/studies/S-EPMC11219989biostudies-literatureUnknown73(9)T cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospotCancer immunology, immunotherapy : CIIIdentification and validation of tumor-specific T cell receptors from tumor infiltrating lymphocytes using tumor organoid co-cultures.PMC1121998932071413 and 82373261Li YLi ZMa LChe XGao ZWang XLiu TBai YSun YZhang QDeng HZhang PfalseIdentification and validation of tumor-specific T cell receptors from tumor infiltrating lymphocytes using tumor organoid co-cultures.T cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospot2024-01-01T00:00:00Z2024 Jul2025-04-04T12:54:48.705Z2025-04-04T12:54:48.705ZS-EPMC112199893895402210.1007/s00262-024-03749-8