Purpose: In the last decade, anticancer agents that act as immune-checkpoint inhibitors have been approved and deployed successfully in treating some cancers such as melanoma, leading to the emergence of immunotherapy as a possible fourth pillar of cancer treatment in addition to surgery, radiotherapy and chemotherapy. For primary brain tumors such as glioblastoma, which show high radioresistance as well as high chemoresistance, there is an urgent need to develop synergistic strategies combining immunotherapy with traditional modalities. The purpose of our work is to develop new combination modalities for glioblastoma which currently has a dismal 5-10% 5-year survival rate.
Methods: Having recently used a commercially available Electric Cell Impedance Sensor (ECIS) to quantify the migration of various cancer cell lines following chemotherapy and following radiotherapy (2 Gy, 10 Gy and 20 Gy) using a cell irradiator, Faxitron CellRad, we now focus on quantifying cell migration following combinations of radiotherapy with temozolomide (TMZ), and other approved immunotherapeutic agents.
Results: Our preliminary results show that irradiated T98G cells (Glioblastoma, brain cancer cells) attach and migrate significantly more (p<0.0001) than non-irradiated cells in the first 20-40 hours post irradiation. Irradiated cells (5 Gy and 20 Gy) show markedly different proliferative and migratory patterns in the course of 7 days following irradiation (Figures 1 and 2 in supplement). Along with clonogenic assays, therapeutic windows suggested by these results will be explored and presented.
Conclusion: Our preliminary results suggest that real time cell migration assays can be used to explore therapeutic windows for optimal combination of immunotherapy and radiotherapy especially in the case of highly radioresistant and chemoresistant cancers such as glioblastoma.