Related Experiment Video
Updated: Jan 18, 2026
Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
Published on: June 27, 2025
Improved identification of tumor-specific TCRs from circulating lymphocytes using autologous colorectal tumor
Lisha Ma1, Xiya Wang2, Qianjing Zhang2
1Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China; Department of Quality Management, the fourth Medical Centre, Chinese PLA General Hospital, Beijing, 100048, China.
Abstract:
The identification of effective T cell receptors (TCRs) with specific reactivity against tumor cells is critical for the efficacy of TCR-engineered T cell therapy. However, different approaches for screening effective TCRs remain to be explored. We developed an optimized approach to identify effective TCRs based on an organoid culture system with patient-derived tumor cells in the presence of oxaliplatin and autologous dendritic cells. By coculturing the immunogenic debris of patient tumor cells from the organoid, we successfully enriched tumor-reactive CD4+ and CD8+ T cells, enhanced the activation and proliferation of T cells, and could facilitate the identification of tumor-reactive CD8+ T cells from patients with MHC I-downregulated tumors. We further used autologous tumor organoids to verify that candidate tumor-specific TCRs can elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells. Our organoid-based tumor-reactive T cell enrichment system and TCR screening validation platform provide an empirical strategy for the isolation of tumor-reactive T cells and can advance the study of TCR-engineered T cell therapy.
Insights
Researchers developed an optimized organoid culture system to identify effective T cell receptors (TCRs) for cancer therapy. This method enriches tumor-reactive T cells, enhancing TCR screening for improved engineered T cell treatments.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Effective T cell receptors (TCRs) are crucial for TCR-engineered T cell therapy efficacy.
- Current methods for screening effective TCRs require further exploration and optimization.
Purpose of the Study:
- To develop and validate an optimized organoid culture system for identifying effective TCRs against tumor cells.
- To enhance the enrichment and identification of tumor-reactive T cells, particularly from patients with MHC I-downregulated tumors.
Main Methods:
- Utilized an organoid culture system with patient-derived tumor cells, oxaliplatin, and autologous dendritic cells.
- Cocultured immunogenic tumor cell debris to enrich tumor-reactive CD4+ and CD8+ T cells.
- Employed autologous tumor organoids to validate candidate tumor-specific TCRs expressed in allogeneic T cells.
Main Results:
- Successfully enriched tumor-reactive CD4+ and CD8+ T cells, enhancing their activation and proliferation.
- Facilitated the identification of tumor-reactive CD8+ T cells from patients with MHC I-downregulated tumors.
- Verified that candidate TCRs elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells.
Conclusions:
- The developed organoid-based system provides an empirical strategy for isolating tumor-reactive T cells.
- This platform advances the study and application of TCR-engineered T cell therapy by improving TCR screening and validation.
- The approach is particularly beneficial for identifying TCRs targeting tumors with reduced MHC I expression.
