Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Mice
2.2. Cell Lines
2.3. Murine Tumor Model
2.4. Histopathologic Analyses
2.5. In Vitro Assay
2.6. Cell Isolation
2.7. Flow Cytometric Analysis
2.8. qRT-PCR
2.9. Measurement of Cytokines
2.10. Killing Assay
2.11. Statistical Analyses
3. Results
3.1. Topical IMQ Exerts an Antitumor Effect through Enhancement of the Immune Response to MC38 Colon Cancer
3.2. IMQ Activates Myeloid Cells, Leading to Upregulation of Costimulatory Molecules and MHC Class II
3.3. Antitumor Effect of IMQ Is Dependent on Adaptive Immunity
3.4. The IMQ-Induced Antitumor Effect Was Dependent on Increased IFN-γ Expression
3.5. IMQ Upregulates Expression of PD-1/PD-L1/PD-L2 in Immune Cells
3.6. IFN-γ Is Not Involved in the IMQ-Induced Upregulation of PD-L1 Expression
3.7. Potent Antitumor Effect of Combination Therapy of Topical IMQ Plus Anti-PD-1 Antibody
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
TLR | Toll-like receptor |
IMQ | Imiquimod |
IFN | Interferon |
TRAIL | Tumor necrosis factor-related apoptosis-inducing ligand |
ITM | In-transit metastasis |
LN | Lymph node |
ORR | Overall response rate |
BSA | Bovine serum albumin |
qRT-PCR | Quantitative reverse transcription-polymerase chain reaction |
PBMC | Peripheral blood mononuclear cell |
GAPDH | Glyceraldehyde-3-phosphate dehydrogenase |
DC | Dendritic cell |
NF-κB | Nuclear factor-kappa B |
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Oya, K.; Nakamura, Y.; Zhenjie, Z.; Tanaka, R.; Okiyama, N.; Ichimura, Y.; Ishitsuka, Y.; Saito, A.; Kubota, N.; Watanabe, R.; et al. Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect. Cancers 2021, 13, 3948. https://doi.org/10.3390/cancers13163948
Oya K, Nakamura Y, Zhenjie Z, Tanaka R, Okiyama N, Ichimura Y, Ishitsuka Y, Saito A, Kubota N, Watanabe R, et al. Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect. Cancers. 2021; 13(16):3948. https://doi.org/10.3390/cancers13163948
Chicago/Turabian StyleOya, Kazumasa, Yoshiyuki Nakamura, Zhu Zhenjie, Ryota Tanaka, Naoko Okiyama, Yuki Ichimura, Yosuke Ishitsuka, Akimasa Saito, Noriko Kubota, Rei Watanabe, and et al. 2021. "Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect" Cancers 13, no. 16: 3948. https://doi.org/10.3390/cancers13163948
APA StyleOya, K., Nakamura, Y., Zhenjie, Z., Tanaka, R., Okiyama, N., Ichimura, Y., Ishitsuka, Y., Saito, A., Kubota, N., Watanabe, R., Tahara, H., Fujimoto, M., & Fujisawa, Y. (2021). Combination Treatment of Topical Imiquimod Plus Anti-PD-1 Antibody Exerts Significantly Potent Antitumor Effect. Cancers, 13(16), 3948. https://doi.org/10.3390/cancers13163948