論文 - 詳細
| RRC ID | 70105 |
|---|---|
| 著者 | Miyamoto T, Murakami R, Hamanishi J, Tanigaki K, Hosoe Y, Mise N, Takamatsu S, Mise Y, Ukita M, Taki M, Yamanoi K, Horikawa N, Abiko K, Yamaguchi K, Baba T, Matsumura N, Mandai M. |
| タイトル | B7-H3 Suppresses Antitumor Immunity via the CCL2-CCR2-M2 Macrophage Axis and Contributes to Ovarian Cancer Progression. |
| ジャーナル | Cancer Immunol Res |
| Abstract |
New approaches beyond PD-1/PD-L1 inhibition are required to target the immunologically diverse tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC). In this study, we explored the immunosuppressive effect of B7-H3 (CD276) via the CCL2-CCR2-M2 macrophage axis and its potential as a therapeutic target. Transcriptome analysis revealed that B7-H3 is highly expressed in PD-L1-low, nonimmunoreactive HGSOC tumors, and its expression negatively correlated with an IFNγ signature, which reflects the tumor immune reactivity. In syngeneic mouse models, B7-H3 (Cd276) knockout (KO) in tumor cells, but not in stromal cells, suppressed tumor progression, with a reduced number of M2 macrophages and an increased number of IFNγ+CD8+ T cells. CCL2 expression was downregulated in the B7-H3 KO tumor cell lines. Inhibition of the CCL2-CCR2 axis partly negated the effects of B7-H3 suppression on M2 macrophage migration and differentiation, and tumor progression. In patients with HGSOC, B7-H3 expression positively correlated with CCL2 expression and M2 macrophage abundance, and patients with B7-H3-high tumors had fewer tumoral IFNγ+CD8+ T cells and poorer prognosis than patients with B7-H3-low tumors. Thus, B7-H3 expression in tumor cells contributes to CCL2-CCR2-M2 macrophage axis-mediated immunosuppression and tumor progression. These findings provide new insights into the immunologic TME and could aid the development of new therapeutic approaches against the unfavorable HGSOC phenotype. |
| 巻・号 | 10(1) |
| ページ | 56-69 |
| 公開日 | 2022-1-1 |
| DOI | 10.1158/2326-6066.CIR-21-0407 |
| PII | 2326-6066.CIR-21-0407 |
| PMID | 34799346 |
| MeSH | Animals B7 Antigens / genetics B7 Antigens / immunology* CD8-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / pathology Cell Line, Tumor Chemokine CCL2 / genetics Female Humans Immune Tolerance Lymphocytes, Tumor-Infiltrating / immunology Macrophages / immunology Mice Mice, Inbred C57BL Mice, Nude Ovarian Neoplasms / immunology* Ovarian Neoplasms / therapy* Receptors, CCR2 / genetics Transcription Factors / metabolism Tumor Microenvironment / immunology Xenograft Model Antitumor Assays |
| IF | 8.728 |
| 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 | 4 |
| 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 | OV2944-HM-1(RCB1483) |