Pancreatic Cancer Organoids Recapitulate Chemotherapy Response and Identify a Potent Cytotoxic T-Cell Population

Area of Science:

• Oncology
• Translational Medicine
• Cancer Biology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) presents significant treatment challenges due to poor outcomes.
• There is a critical need for precision-based therapeutic strategies tailored to individual patients.

Purpose of the Study:

• To establish and utilize patient-derived organoids (PDOs) for predicting effective combination therapies in PDAC.
• To evaluate the potential of autologous tumor-infiltrating lymphocytes (TILs) in conjunction with PDOs.

Main Methods:

• Established autologous αβ and γδ-enriched TIL and PDO cultures from PDAC tissue.
• Characterized PDOs via immunostaining, next-generation sequencing, and drug screening.
• Assessed TIL functionality and potency against autologous PDOs using flow cytometry and sequencing.

Main Results:

• Achieved an 80% success rate in PDO culture establishment within 36 days, recapitulating tumor features.
• PDO drug sensitivity correlated with patient serum CA 19-9 levels and recurrence-free survival.
• γδ-enriched TILs showed enhanced activation of αβ T cells and potent anti-PDO activity; γδ T cell infiltration correlated with improved survival.

Conclusions:

• Confirmed the feasibility of generating PDOs within a clinically relevant timeframe.
• Demonstrated the utility of PDOs for predicting therapeutic success in PDAC.
• Highlighted the potential role of γδ T cells in enhancing anti-PDAC immunity.