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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1481129
This article is part of the Research Topic Adaptive Immune Biomarker Signature for Cancer View all 5 articles

IAPP blocks anti-breast cancer function of CD8 + T cells via targeting cuproptosis

Provisionally accepted
Dandan Guo Dandan Guo 1Zhijian Huang Zhijian Huang 2Qianqian Wang Qianqian Wang 1Wei Chen Wei Chen 1Yu Huang Yu Huang 1Xinhao Sun Xinhao Sun 3Jian Chen Jian Chen 2Shuying Feng Shuying Feng 1*
  • 1 Henan University of Chinese Medicine, Zhengzhou, Henan Province, China
  • 2 Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
  • 3 Department of Thyroid and Breast Surgery, Ningde Municipal Hospital of Ningde Normal University, Ningde 352100, China, Ningde, Fujian Province, China

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

    Background: Breast cancer (BRCA) is the most prevalent type of cancer worldwide.As a highly heterogeneous cancer, it has a high recurrence rate. Since its biological behavior can be regulated by immunity and cuprotosis, so exploring potential therapeutic targets to mediate immunity and cuprotosis is of great significance for BRCA therapy.The immune-related genes and immune-cuprotosis-related deferentially expressed genes (ICR-DEGs) were identified by mining the TCGA database. Prognostic analysis, differential expression analysis, univariate and lasso regression analyses were used to determine their independent prognostic values. To evaluate the relationship between ICR-DEGs and immune scores, we constructed a prognostic risk model to evaluate immune checkpoints, and then the role of tumor immune microenvironment in BRCA was explored. Furthermore, anti-BRCA function and mechanism of islet amyloid poly-peptide (IAPP) mediated CD8 + T cells were verified by means of flow cytometry, ELISA, and subcutaneous transplantation tumor model.All results suggested that immune-cuprotosis-related genes were a potential predictor of BRCA's response to immune checkpoint inhibitors and immunotherapy biomarkers. Thereby downregulation of IAPP reduced cuprotosis of CD8 + T or Her2-CAR-T cells to promote the anti-BRCA function both in vitro and in vivo.Our research had clarified the function and mechanism of IAPP in CD8 + T cells, providing new ideas for improving the diagnosis and treatment of BRCA.

    Keywords: breast cancer, IAPP, Cuprotosis, biomarkers, ICR-DEGs

    Received: 15 Aug 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Guo, Huang, Wang, Chen, Huang, Sun, Chen and Feng. 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: Shuying Feng, Henan University of Chinese Medicine, Zhengzhou, 450008, Henan Province, China

    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.