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Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
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Tumor organoid-T-cell coculture systems
Chiara M Cattaneo1,2, Krijn K Dijkstra1,2, Lorenzo F Fanchi1
1Department of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
Nature Protocols
|December 20, 2019
Summary
This study introduces a novel method to expand tumor-reactive T cells from patient samples using tumor organoids. This approach facilitates personalized cancer immunotherapy research by enabling ex vivo assessment of T-cell function.
Area of Science:
- Immunology
- Oncology
- Cancer Immunotherapy
Background:
- T cells are crucial for effective cancer immunotherapy.
- Current methods for expanding tumor-specific T cells and studying their interactions with patient tumors are limited.
- Personalized approaches are needed to improve T-cell-based cancer treatments.
Purpose of the Study:
- To develop and assess a method for generating and functionally evaluating tumor-reactive T cells from individual patients.
- To establish an ex vivo system for studying T-cell responses against patient-derived tumors.
- To enable antigen-agnostic expansion of T cells targeting specific tumor types.
Main Methods:
- Coculture of tumor organoids with autologous peripheral blood lymphocytes for T-cell expansion.
- Initial 2-week coculture with IFNγ-stimulated autologous tumor cells to expand tumor-reactive T cells.
- Functional assessment of T cells for IFNγ secretion, degranulation, and tumor organoid killing capacity.
Main Results:
- Successful generation of tumor-reactive CD8+ T-cell populations from ~33-50% of non-small-cell lung cancer (NSCLC) and microsatellite-instable colorectal cancer (CRC) patient samples within 2 weeks.
- Demonstrated capacity of expanded T cells to recognize tumor cells and mediate effector functions.
- Validated ability of T cells to kill tumor organoids in vitro.
Conclusions:
- The described coculture strategy effectively generates patient-specific tumor-reactive T cells.
- This method provides a valuable ex vivo platform for testing T-cell-based immunotherapies tailored to individual patients.
- The antigen-agnostic approach offers a versatile tool for advancing personalized cancer treatment.
