Amlexanox enhances the antitumor effect of anti-PD-1 antibody
| Autor: | Koji Yano, Kaoru Yamada, Akio Kihara, Kazuhiko Takeda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cytotoxic T cell medicine.drug_class T cell medicine.medical_treatment Programmed Cell Death 1 Receptor Biophysics Aminopyridines Cancer immunotherapy Monoclonal antibody Biochemistry Jurkat cells B7-H1 Antigen Interferon-gamma Jurkat Cells 03 medical and health sciences 0302 clinical medicine Interferon Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Molecular Biology Cancer Mice Inbred BALB C Chemistry Immunity Antibodies Monoclonal Dendritic Cells Neoplasms Experimental Cell Biology Mixed lymphocyte reaction Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Amlexanox 030220 oncology & carcinogenesis Cancer research Female Interferon-γ Lymphocyte Culture Test Mixed T-Lymphocytes Cytotoxic medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 560:1-6 |
| ISSN: | 0006-291X |
| Popis: | Cancer immunotherapy, especially treatment with monoclonal antibodies (mAbs) that block programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling, has attracted attention as a new therapeutic option for cancer. However, only a limited number of patients have responded to this treatment approach. In this study, we searched for compounds that enhance the efficacy of anti-PD-1 mAb using mixed lymphocyte reaction (MLR), which is a mixed culture system of the two key cells (dendritic and T cells) involved in tumor immunity. We found that amlexanox enhanced production of interferon (IFN)-gamma, an indicator of T cell activation, by anti-PD-1 mAb. Amlexanox also induced PD-L1 expression in dendritic cells in MLR, whereas it did not stimulate interleukin-2 production by Jurkat T cells. These results suggest that amlexanox acts on dendritic cells, not T cells, in MLR. Furthermore, it enhanced the antitumor effect of the anti-PD-1 mAb in vivo in a mouse tumor-bearing model. The combination of amlexanox and anti-PD-1 mAb increased the expression of Ifng encoding IFN-gamma, IFN-gamma-related genes, Cd274 encoding PD-L1, and cytotoxic T cell-related genes in tumors. In conclusion, amlexanox stimulates the antitumor effect of anti-PD-1 mAb by acting on dendritic cells, which in turn activates cytotoxic T cells in tumors. |
| Databáze: | OpenAIRE |
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