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BP23. Assessment of Tumor Infiltrating Lymphocyte therapy for metastatic epithelial cancers using Patient Derived Tumor Organoids

Friday, March 6, 2026
2:12 PM - 2:19 PM MST
Location: 301A
Introduction: Adoptive cell transfer of neoantigen specific tumor infiltrating lymphocytes (TIL) has the ability to mediate responses in patients with metastatic epithelial cancers.  While some identified factors are associated with response, there is a need for ways to determine which patients will benefit from treatment with TIL.  Patient derived tumor organoids (PDTO) retain the genetic makeup of the tumor from which they are derived and are a useful tool in personalized medicine to test the effectiveness of anti-cancer therapies.  While organoids have been used to assess CAR-T cells and immune checkpoint inhibitors, their use in TIL therapy has been less explored. Organoids are an ideal ex vivo reagent as they retain tumor-specific antigen processing and presentation. We therefore examined whether organoid reactivity could predict clinical response after TIL therapy


Methods:

Tumor organoids and TIL were grown from patients with metastatic epithelial cancers treated on a TIL protocol from June 2022 to January 2025.  Cocultures of autologous PDTO and CD8+ enriched TIL infusion products were performed. Reactivity of TIL was analyzed by interferon gamma secretion as measured by ELISpot and 4-1BB upregulation measured by flow cytometry.  Positive recognition of PDTO by TIL was defined as 4-1BB% more than double background and greater than 3%. Patient clinical response was measured using Response Evaluation Criteria in Solid Tumors 1.0. 


Results:

Final TIL infusion products from thirty treated patients were tested against their PDTO. The most common histologies were colorectal (21 patients, 70%), pancreatic (4 patients, 13%), and breast (2 patients, 7%) cancer. Of 15 patients whose infusion product showed organoid recognition, 8 achieved objective responses (53%) while only one patient without organoid recognition responded (7%; p=0.014). The median 4-1BB expression after coculture from responders and non-responders were 10.9% and 1.4%, respectively (p=0.0377). Patients with organoid reactive TIL were more likely to exhibit tumor shrinkage after treatment (Figure 1).


Conclusions:

In vitro TIL reactivity against autologous tumor organoid appears to be associated with objective clinical response in patients with metastatic epithelial cancers.  Despite only accounting for CD8+ reactivities, there was still a strong correlation between organoid recognition and clinical response. Organoids have the potential to be a valuable pre-clinical reagent to test adoptive cell therapy efficacy and further study T-cell mediated tumor rejection.

Learning Objectives:

  • Participants should have understanding of how patient derived tumor organoids can be used to evaluate adoptive cell therapies.
  • Participants should understand that organoids are mainly used to assess CD8+ T cell reactivities, and that reactivity correlates with clinical response.