Purpose: Temozolomide (TMZ) is the most frequent adjuvant chemotherapy drug in gliomas. PDL1 expresses on various tumors, including gliomas, and anti-PD-1 antibodies have been approved for treating some tumors by FDA. This study was to evaluate the therapeutical potential of combined TMZ with anti-PD-1 antibody therapy for mouse orthotopic glioma model.
Methods: We performed C57BL/6 mouse orthotopic glioma model by stereotactic intracranial implantation of glioma cell line GL261, mice were randomly divided into four groups: (1) control group; (2) TMZ group; (3) anti-PD-1 antibody group; (4) TMZ combined with anti-PD-1 antibody group. Then the volume or size of tumor was assessed by 7.0 T MRI and immunohistochemistry, and the number of CD4 and CD8 infiltrating cells in brain tumor and spleen was evaluated by immunohistochemistry. Western blot was used to evaluate the expression of PDL1. Furthermore, Overall survival of each group mice was also evaluated.
Results: Overall survival was significantly improved in combined group compared to other groups (χ2 = 32.043, p < 0.01). The volume or size of tumor was significantly decreased in combined group compared with other groups (F = 42.771, P < 0.01). And the number of CD4 and CD8 infiltrating cells in brain tumor was also obviously increased in combined group (CD4 F = 45.67, P < 0.01; CD8 F = 53.75, P < 0.01).
Conclusion: Anti-PD1 antibody combined with TMZ therapy for orthotopic mouse glioma model could significantly improve the survival time of tumor-bear mice. Thus, this study provides the effective preclinical evidence for support clinical chemotherapy combined with immunotherapy for glioma patients.
Keywords: Chemotherapy; Glioma; Immunotherapy; PD-1 Antibody; Temozolomide.
Copyright © 2018 Elsevier Inc. All rights reserved.