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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1389387

Zinc dampens anti-tumor immunity by promoting Foxp3+ regulatory T cells

Provisionally accepted
Sugandha Narayan Sugandha Narayan Rajdeep Dalal Rajdeep Dalal Zaigham Abbas Rizvi Zaigham Abbas Rizvi Amit Awasthi Amit Awasthi *
  • Translational Health Science and Technology Institute (THSTI), Faridabad, India

The final, formatted version of the article will be published soon.

    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. Our findings show that high dietary Zn promotes tumor progression by fostering a pro-tumorigenic environment mediated by T cells. In contrast, deficiency in dietary Zn and chelation of tissue Zn emerge as potent drivers of antitumor immunity. We elucidated that increased Zn intake facilitates tumor progression by fostering Foxp3+ regulatory T cells (Tregs) frequency. Remarkably, we have pinpointed FOXO1 as the master regulator governing the influence of Zn on Tregs, elucidating a novel mechanistic insight. Finally, we introduce a promising therapeutic approach by showing that administering Clioquinol (CQ) significantly enhances αPD-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.

    Keywords: cancer immunotherapy, Checkpoint inhibition therapy, Zinc, Treg - regulatory T cell, Cancer, FoxO1, antitumor immunity

    Received: 21 Feb 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Narayan, Dalal, Rizvi and Awasthi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Amit Awasthi, Translational Health Science and Technology Institute (THSTI), Faridabad, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.