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胰岛淀粉样多肽通过靶向铜死亡来阻断CD8T细胞的抗乳腺癌功能。

IAPP blocks anti-breast cancer function of CD8T cells via targeting cuproptosis.

作者信息

Guo Dandan, Huang Zhijian, Wang Qianqian, Chen Wei, Huang Yu, Sun Xinhao, Chen Jian, Feng Shuying

机构信息

Medical College, Henan University of Chinese Medicine, Zhengzhou, China.

Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou, China.

出版信息

Front Immunol. 2024 Nov 25;15:1481129. doi: 10.3389/fimmu.2024.1481129. eCollection 2024.

DOI:10.3389/fimmu.2024.1481129
PMID:39654888
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11625781/
Abstract

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 target to mediate immunity and cuprotosis is of great significance for BRCA therapy.

METHODS

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 CD8T cells were verified by means of flow cytometry, ELISA, and subcutaneous transplantation tumor model.

RESULTS

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 CD8T or Her2CAR-T cells to promote the anti-BRCA function both and .

CONCLUSION

Our research had clarified the function and mechanism of IAPP in CD8T cells, providing new ideas for improving the diagnosis and treatment of BRCA.

摘要

背景

乳腺癌（BRCA）是全球最常见的癌症类型。作为一种高度异质性的癌症，其复发率很高。由于其生物学行为可受免疫和铜死亡调节，因此探索介导免疫和铜死亡的潜在治疗靶点对BRCA治疗具有重要意义。

方法

通过挖掘TCGA数据库鉴定免疫相关基因和免疫铜死亡相关差异表达基因（ICR-DEGs）。采用预后分析、差异表达分析、单变量和套索回归分析来确定其独立预后价值。为了评估ICR-DEGs与免疫评分之间的关系，我们构建了一个预后风险模型来评估免疫检查点，进而探讨肿瘤免疫微环境在BRCA中的作用。此外，通过流式细胞术、酶联免疫吸附测定和皮下移植瘤模型验证胰岛淀粉样多肽（IAPP）介导的CD8T细胞的抗BRCA功能及机制。

结果

所有结果表明，免疫铜死亡相关基因是BRCA对免疫检查点抑制剂反应的潜在预测指标和免疫治疗生物标志物。因此，IAPP的下调降低了CD8T或Her2CAR-T细胞的铜死亡，从而促进了两者的抗BRCA功能。

结论

我们的研究阐明了IAPP在CD8T细胞中的功能和机制，为改善BRCA的诊断和治疗提供了新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/3c585d5bff35/fimmu-15-1481129-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/a8de95d634ce/fimmu-15-1481129-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/bb536de599c4/fimmu-15-1481129-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/4a1fdc804c6b/fimmu-15-1481129-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/807983f9acf1/fimmu-15-1481129-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/22dc82fedf38/fimmu-15-1481129-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/ac5b64aa7c6c/fimmu-15-1481129-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/0e770c8c090b/fimmu-15-1481129-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/3c585d5bff35/fimmu-15-1481129-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/a8de95d634ce/fimmu-15-1481129-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/bb536de599c4/fimmu-15-1481129-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/4a1fdc804c6b/fimmu-15-1481129-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/807983f9acf1/fimmu-15-1481129-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/22dc82fedf38/fimmu-15-1481129-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/ac5b64aa7c6c/fimmu-15-1481129-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/0e770c8c090b/fimmu-15-1481129-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8de5/11625781/3c585d5bff35/fimmu-15-1481129-g008.jpg

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