Deleting the TFG-β receptor in NK cells overcame immune suppression and enabled anti-tumor activity in preclinical models.
Preclinical research from The University of Texas MD Anderson Cancer Center finds that although glioblastoma stem cells (GSCs) can be targeted by natural killer (NK) cells, they are able to evade immune attack by releasing the TFG-β signaling protein, which blocks NK cell activity. Deleting the TFG-β receptor in NK cells, however, rendered them resistant to this immune suppression and enabled their anti-tumor activity.
The findings, published today (June 17, 2021) in the Journal of Clinical Investigation, suggest that engineering NK cells to resist immune suppression may be a feasible path toward using NK cell-based immunotherapies for treating glioblastoma.
“There is tremendous interest in utilizing immunotherapy to improve treatments for patients with glioblastoma, but there has been limited success to date,” said senior author Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy. “We were able to overcome the immunosuppressive environment in the brain by genetically engineering NK cells, which were then able to eliminate the tumor-regenerating GSCs. We are encouraged by these early results and hope to apply similar strategies to explore NK cell therapies in additional solid tumor types.”
Glioblastoma is the most common and aggressive form of primary brain tumor in adults. Current treatments are only effective for a short time, with recurrences driven largely by small populations of therapy-resistant GSCs. Therefore, developing new treatments that can effectively target GSCs is necessary.
Published data suggests that NK cells may be capable of targeting GCSs, but it was unclear whether the stem cells would indeed be susceptible to NK-cell killing, Rezvani explained. Therefore, her team designed the study to evaluate how effective NK cells may be against GSCs.