論文 - 詳細
| RRC ID | 78164 |
|---|---|
| 著者 | Hu X, Shui Y, Hirano H, Kusano K, Guo WZ, Fujino M, Li XK. |
| タイトル | PD-L1 antibody enhanced β-glucan antitumor effects via blockade of the immune checkpoints in a melanoma model. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
In the tumor microenvironment (TME), one of the major functions of tumor-recruited CD11b+ cells are the suppression of the T-cell-mediated anti-tumor immune response. β-glucan could convert the phenotype of tumor-recruited CD11b+ cells from the suppressive to the promotive, and enhanced their anti-tumor effects. However, β-glucan could enhance the PD-1/PD-L1 expression on CD11b+ cells, while PD-1 could inhibit macrophage phagocytosis and PD-L1 could induce a co-inhibitory signal in T-cells and lead to T-cell apoptosis and anergy. These protumor effects may be reversed by PD-1/PD-L1 block therapy. In the present study, we focused on the efficacy of β-glucan anti-tumor therapy combined with anti-PD-L1 mAb treatment, and the mechanism of their synergistic effects could be fully verified. We verified the effect of β-glucan (i.e., inflammatory cytokine secretion of TNF-α, IL-12, IL-6, IL-1β and the expression of immune checkpoint PD-1/PD-L1) in naïve mouse peritoneal exudate CD11b+ cells. In our mouse melanoma model, treatment with a PD-L1 blocking antibody with β-glucan synergized tumor regression. After treatment with β-glucan and anti-PD-L1 mAb antibody, tumor infiltrating leukocyte (TILs) not only showed a competent T-cell function (CD107a, perforin, IL-2, IFN-γ and Ki67) and CTL population, but also showed enhanced tumor-recruited CD11b+ cell activity (IL-12, IL-6, IL-1β and PD-1). This effect was also verified in the peritoneal exudate CD11b+ cells of tumor-bearing mice. PD-1/PD-L1 blockade therapy enhanced the β-glucan antitumor effects via the blockade of tumor-recruited CD11b+ cell immune checkpoints in the melanoma model. |
| 巻・号 | 72(3) |
| ページ | 719-731 |
| 公開日 | 2023-3-1 |
| DOI | 10.1007/s00262-022-03276-4 |
| PII | 10.1007/s00262-022-03276-4 |
| PMID | 36053290 |
| MeSH | Animals Antibodies, Monoclonal / pharmacology B7-H1 Antigen Cell Line, Tumor Interleukin-12 / pharmacology Interleukin-6* Melanoma* Mice Programmed Cell Death 1 Receptor Tumor Microenvironment |
| IF | 5.442 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16F10(RCB2630) |