Abstract
Glioblastoma is the most frequent primary brain tumor, with a dismal median survival rate of approximately 15 months despite the current standard of care that includes surgery, radiotherapy and chemotherapy. The recent success of immune checkpointinhibitors in treating metastatic melanoma and non-small-cell lung cancer has led to their evaluation in various clinical trials for potential use against glioblastoma. This in vitro study aimed to assess the combination of pembrolizumab, a PD-1 immune checkpoint inhibitor, and radiotherapy for its possible use in treating glioblastoma.
Utilizing a Faxitron CellRad cell irradiator, Electric Cell Impedance Sensor (ECIS), Flourescence Microscopy, and Clonogenic Assay, we quantified the migration, barrier function, and death of glioblastoma cells (T98G and U87) following exposure to radiotherapy alone and both radiotherapy and immunotherapy with pembrolizumab. Cell survival reduces significantly as radiation dose increases relative to untreated T98G cells, from 2 Gy (p < 0.05) to 50 Gy (? < 1 × 10−14). Increasing doses weaken cell-cell adhesion, a trigger for metastasis (p < 0.05). Additionally, we observe no statistically significant differences in cell migration, cell-cell adhesion and cell death between the group treated with pembrolizumab and radiation doses at 5 Gy and 20 Gy and the group treated with radiation alone or pembrolizumab alone for both T98G and U87 cell lines.
Our combined treatment of pembrolizumab and radiation therapy did not significantly affect cell migration, cell-cell adhesion and cell survival (p < 0.05). Our multimodal in vitro testing serves as a platform that could be upgraded by addition of immune system components to provide useful cellular level insights into therapeutic windows for improved brain tumor treatment outcomes.