Interactions between Ɣẟ T-Cell subclass and patient derived pancreas cancer tumor organoid models indicate potential for cell-mediated intervention in PDAC

 

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B981
Abstract ID: 7964

Presenting Author:
Devin M Burpee , Undergraduate Researcher at Univ. of Wisconsin Carbone Cancer Ctr.

Abstract:

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer resistant to immunotherapy (IO). Suboptimal models of immune response within the tumor microenvironment (TME) limit new IO development. Ɣẟ T-Cells (ƔẟT), are overrepresented within the PDAC TME. We investigated the role of ƔẟT in PDAC TME, developing a new system to model immune interactions. ƔẟT serve as a potential allogeneic cellular therapy without significant risk for graft-versus-host effect.

Methods: ƔẟTs isolated from peripheral blood of healthy donors were expanded in low-dose IL-2, zoledronate, and brief activation (CD3/CD28 co-stimulation). To evaluate cytotoxicity of expanded ƔẟT, live cell imaging of a patient-derived organoid model was used. Tumor biopsies (n=3) were obtained from consented patients, generating 3D Pancreas Cancer Organoids (PCOs). ƔẟT were co-incubated with PDAC PCOs. Cleaved caspase 3/7 dye and DNA intercalating dye (TOPRO-3) were added 48 hours later. The percentage of each organoid’s area marked by caspase dye and TOPRO-3 were calculated.

Conclusions: ƔẟT proliferate rapidly ex vivo (~50x in 21 days), maintaining effector function. ƔẟT efficiently infiltrate PCOs. Using PCOs ex vivo, we demonstrate that ƔẟT retain cytotoxicity against PDAC, with ability to induce apoptosis exceeding that of FOLFIRINOX chemotherapy. Future work centers around using this model system to interrogate and unlock mechanisms to further potentiate the cytolytic capacity of ƔẟT against PDAC.