Glioblastoma is the most common primary brain tumor. The current standard therapy for patients with glioblastoma is surgery and combination of radiotherapy with temozolomide chemotherapy. However, the prognosis is still very poor. Much research has been done to improve patient outcomes in glioblastoma. Recently, immunotherapy with immune checkpoint inhibitors, such as ipilimumab, nivolumab, and pembrolizumab shows great clinical improvements in other advanced tumors, which make immunotherapy an attractive strategy in glioblastoma treatment.
The expression of PD-L1 was determined by flow cytometry. The concentration of adriamycin was determined by CCK-8 assay depending on the inhibition rate of U251 cells, which was set to less then 50%(IC50). After treatment with different concentrations of adriamycin, cell proliferation of T lymphocytes was detected by CCK-8 method, cell apoptosis of T lymphocytes and PD-L1 expression were analyzed by flow cytometry. Treated with different concentrations of adriamycin alone or in combination with PD-L1 inhibitors, U251 cells and T lymphocyte proliferation in co-culture were determined by CCK-8 assay.
The expression of PD-L1 was nearly 70%. The IC50 of adriamycin was 4.298mg/L. Adriamycin could enhance the proliferation of T lymphocytes when concentration was less than 4.298mg/L and could up-regulate the expression of PD-L1. Adriamycin (4.298mg/L) combined with immunotherapy (PD-L1 inhibitor 1.5mg/L) could inhibit glioma cells growth obviously and the number of dead T lymphocytes in co-culture system was reduced.
Adriamycin combined with immunotherapy (PD-L1 inhibitor) is a promising strategy for glioma treatment and our research provides theoretical basis for combination of adriamycin and immunotherapy in glioma treatment.
Clinical trial identification
Legal entity responsible for the study
Laboratory for Experimental Medicine and Surgery of Southeast University
All authors have declared no conflicts of interest.