Zinc dampens antitumor immunity by promoting Foxp3 + regulatory T cells.
| Autor: | Narayan S; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India., Dalal R; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India., Rizvi ZA; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India.; Immunology Core Lab, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India., Awasthi A; Centre for Immunobiology and Immunotherapy, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India.; Immunology Core Lab, Translational Health Science and Technology Institute, National Capital Region (NCR)-Biotech Science Cluster, Faridabad, Haryana, India. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2024 Aug 23; Vol. 15, pp. 1389387. Date of Electronic Publication: 2024 Aug 23 (Print Publication: 2024). |
| DOI: | 10.3389/fimmu.2024.1389387 |
| Abstrakt: | Introduction: The role of zinc (Zn) in tumor development and immune modulation has always been paradoxical. This study redefines our understanding of the impact of Zn on cancer progression and therapeutic strategies. Methods: We investigated the effects of dietary Zn levels on tumor progression and immune responses. This included examining the impact of both high and deficient dietary Zn, as well as Zn chelation, on tumor growth and immune cell populations. Specifically, we analyzed the frequency of Foxp3 + regulatory T-cells (Tregs) and identified the role of FOXO1 in Zn-mediated effects on Tregs. Additionally, we explored the therapeutic potential of clioquinol (CQ) in enhancing α -PD-1 immunotherapy responses, particularly in melanoma. Results: Our findings show that high dietary Zn promotes tumor progression by fostering a protumorigenic environment mediated by T cells. Increased Zn intake was found to facilitate tumor progression by increasing Foxp3 + Treg frequency. In contrast, deficiency in dietary Zn and chelation of tissue Zn emerged as potent drivers of antitumor immunity. We pinpointed FOXO1 as the master regulator governing the influence of Zn on Tregs. Discussion: These results reveal a novel mechanistic insight into how Zn influences tumor progression and immune regulation. The identification of FOXO1 as a key regulator opens new avenues for understanding the role of Zn in cancer biology. Furthermore, we introduce a promising therapeutic approach by showing that administering clioquinol (CQ) significantly enhances α -PD-1 immunotherapy response, particularly in melanoma. These revelations transform our comprehension of the multifaceted role of Zn in tumorigenesis and immune regulation, highlighting innovative possibilities for cancer therapy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Narayan, Dalal, Rizvi and Awasthi.) |
| Databáze: | MEDLINE |
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