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Cellular and Molecular Bioengineering

Cellular and Molecular Bioengineering - Poster Session E

Poster I15 - Unveiling the Hidden Signals: Profiling Pancreatic Tumor Spheroids for Modulators of NK Cells Post Radiotherapy

Saturday, October 26, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

DJ

Daniel Juan

Student
University of Pennsylvania
Rockville, Maryland, United States

Co-Author(s)

AT

ALfredo Tovar Walker

Graduate Student
University of Pennsylvania, United States
AN

Akeem Ngomu Akilimali

Senior Research Investigator
University of Pennsylvania Perelman School of Medicine, United States
CJ

Carl June

Richard W. Vague Professor
University of Pennsylvania Perelman School of Medicine, United States

Last Author(s)

NS

Neil Sheppard, D.Phil

Adjunct Associate Professor of Pathology & Laboratory Medicine
University of Pennsylvania Perelman School of Medicine, United States

Introduction: Natural killer (NK) cells can eliminate cancer cells through non-MHC-restrictive mechanisms, making them promising for combination therapies with treatments like radiotherapy. Radiotherapy induces stress in solid pancreatic tumor cells, leading to the upregulation of stress ligands and secretion of pro-inflammatory cytokines and chemokines, which enhance NK cell antitumor activity. Despite this, tumor spheroid responses to ionizing radiation remain underexplored. We aim to characterize the response of non-ablative ionizing radiation on pancreatic tumor spheroids as a translational model to study efficacy and mechanisms of radiotherapy-NK cell therapy combination.

Materials and

Methods: Tumor spheroids from AsPC-1, HPAC, and BxPC3 cell lines were formed on non-adherent 96-well plates and irradiated with 0, 2, 4, 8-Gy doses using an X-ray irradiator. Spheroids were monitored and dissociated every 24 h up to 96 h post-irradiation, with cell viability and count assessed with viability staining via flow cytometry and CellTiter-Glo assay.

Results, Conclusions, and Discussions: AsPC-1 counts steadily decreased with increasing radiation dose for all timepoints, HPAC counts also consistently decreased at doses ≥ 4 Gy, and BxPC3 counts decreased at 2 Gy but not at higher doses at 24 h and decreased across all doses at timepoints ≥ 48 h. Untreated tumor spheroids continued to proliferate up to 96 h. The data confirms all studied cell lines as radiosensitive, demonstrating complex radiosensitivity profiles across doses and timepoints. The sufficient spheroid viability allows downstream assays, and more replicates are needed to explore variability. These results support tumor spheroids as a potential model for studying the combination of radiotherapy and NK cell therapy.

Acknowledgements (Optional): I would like to express my sincere gratitude to Alfredo Tovar Walker, Dr. Akeem Ngomu Akilimali, Dr. Neil Sheppard and the rest of the June/THINK Lab for nurturing scientific curiosity and providing mentorship. Additionally, I am grateful to the faculty involved in the University of Pennsylvania Perelman School of Medicine Summer Undergraduate Internship Program (SUIP) for the opportunity to conduct impactful cancer research.