| Autor: |
Keying Che, Yuting Luo, Xueru Song, Zhe Yang, Hanbing Wang, Tao Shi, Yue Wang, Xuan Wang, Hongyan Wu, Lixia Yu, Baorui Liu, Jia Wei |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EMBO Molecular Medicine, Vol 16, Iss 2, Pp 251-266 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1757-4684 |
| DOI: |
10.1038/s44321-023-00012-y |
| Popis: |
Abstract Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME) that limits the effects of immunotherapy. This study aimed to investigate the immunomodulatory effects of intraperitoneal administration of IL-33, a cytokine that is reported to potentiate antitumor immunity and inhibit metastasis. We found survival was significantly prolonged in patients with high IL-33 mRNA expression. In immunocompetent mice, intraperitoneal administration of IL-33 could induce a celiac inflammatory environment, activate immunologic effector cells, and reverse the immunosuppressive tumor microenvironment, which effectively delayed tumor progression and PM of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 signaling. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) had a synergistic antitumor effect. Inducing a local inflammatory milieu by IL-33 administration provided a novel approach for treating peritoneal metastasis, which, when combined with TAM reprogramming to reshape TIME, can achieve better treatment efficacy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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