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Published VersionCC BY-NC-ND V4.0, Open Access
Journal article
Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine IFNα and is enhanced by CD47 blockade
Scientific Reports, Vol.15(1), pp.1-17
2025
PMID: 39885296
Abstract
Previously, we demonstrated that natural host-defence peptide caerin 1.1/caerin 1.9 (F1/F3) increases the efficacy of anti-PD-1 and therapeutic vaccine, in a HPV16 + TC-1 tumour model, but the anti-tumor mechanism of F1/F3 is still unclear. In this study, we explored the impact of F1/F3 on the tumor microenvironment in a transplanted B16 melanoma model, and further investigated the mechanism of action of F1/F3 using monoclonal antibodies to deplete relevant cells, gene knockout mice and flow cytometry. We show that F1/F3 is able to inhibit the growth of melanoma B16 tumour cells both in vitro and in vivo. Depletion of macrophages, blockade of IFNα receptor, and Stat1 inhibition each abolishes F1/F3-mediated antitumor responses. Subsequent analysis reveals that F1/F3 increases the tumour infiltration of inflammatory macrophages, upregulates the level of IFNα receptor, and promotes the secretion of IFNα by macrophages. Interestingly, F1/F3 upregulates CD47 level on tumour cells; and blocking CD47 increases F1/F3-mediated antitumor responses. Furthermore, F1/F3 intratumor injection, CD47 blockade, and therapeutic vaccination significantly increases the survival time of B16 tumour-bearing mice. These results indicate that F1/F3 may be effective to improve the efficacy of ICB and therapeutic vaccine-based immunotherapy for human epithelial cancers and warrants consideration for clinical trials.
Details
- Title
- Caerin 1.1/1.9-mediated antitumor immunity depends on IFNAR-Stat1 signalling of tumour infiltrating macrophage by autocrine IFNα and is enhanced by CD47 blockade
- Authors
- Junjie Li - Guangdong Pharmaceutical UniversityYuandong Luo - Guizhou UniversityQuanlan Fu - Guizhou UniversityShuxian Tang - First People's Hospital of FoshanPingping Zhang - First People's Hospital of FoshanIan H Frazer - The University of QueenslandXiaosong Liu - First People's Hospital of FoshanTianfang Wang (Corresponding Author) - University of the Sunshine Coast, Queensland, Centre for BioinnovationGuoying Ni (Corresponding Author) - First People's Hospital of Foshan
- Publication details
- Scientific Reports, Vol.15(1), pp.1-17
- Publisher
- Nature Publishing Group
- Date published
- 2025
- DOI
- 10.1038/s41598-025-87687-0
- ISSN
- 2045-2322; 2045-2322
- PMID
- 39885296
- Copyright note
- This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
- Data Availability
- The flow cytometry (FCS) files associated with the figures in this manuscript are available on the Zenodo portal as follows: Fig. 1D and S2A–C: https://doi.org/10.5281/zenodo.13976956; Figs. 2E,F, 3B,D,E: https://doi.org/10.5281/zenodo.13977048; Fig. 3C, 4B and S2D: https://doi.org/10.5281/zenodo.13977117; Fig. 3H: https://doi.org/10.5281/zenodo.13977179; Fig. 5F–J,N,O: https://doi.org/10.5281/zenodo.13977209; Fig. 6B_1: https://doi.org/10.5281/zenodo.13977284; Fig. 6B_2: https://doi.org/10.5281/zenodo.13977309; Fig. 6C: https://doi.org/10.5281/zenodo.13983390. The datasets used and analysed during the current study available from the corresponding author on reasonable request.
- Grant note
- This study was supported in part by the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong Science and Technology Department (2016A020213001), National Science Foundation of Guangdong province (2020A1515010855), National Science Foundation of China (31971355), The Deng Feng Project of First People’s Hospital of Foshan (2019A008).
- Organisation Unit
- School of Science and Engineering - Legacy; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991100144302621
- Output Type
- Journal article
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