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白细胞介素-7通过JAK1/STAT3信号通路调控单核细胞趋化蛋白-1，从而增强非小细胞肺癌中髓源性抑制细胞的募集。

Interleukin-7 enhances recruitment of MDSCs by regulating MCP-1 via JAK1/STAT3 signaling pathway in non-small cell lung cancer.

作者信息

Cheng Huan, Shao Yajiao, Zhang Ao, Li Caixia, Li Xinxin, Fu Yuxin, Ming Jian

机构信息

Department of Pathology, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenhe District, Shenyang, 110016, Liaoning, China.

Post-graduate College, China Medical University, No.77, Puhe Road, Shenbei District, Shenyang, 110122, Liaoning, China.

出版信息

Sci Rep. 2025 May 15;15(1):16869. doi: 10.1038/s41598-025-01868-5.

DOI:10.1038/s41598-025-01868-5
PMID:40374882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081855/
Abstract

Lung cancer is one of the most commonly diagnosed cancers worldwide and the leading cause of cancer-related deaths worldwide. In recent years, an increasing number of studies have shown that the tumor immune microenvironment (TIME) has a significant impact on the development of lung cancer. Interleukin-7 (IL-7) is an essential cytokine for the adaptive immune system and plays an important immunoregulatory role in different types of tumors. However, the relationship between IL-7 and TIME in non-small cell lung cancer (NSCLC) is not yet known. This study found that the expression of MCP-1 and CD11b was correlated with the expression of IL-7/IL-7R. MCP-1, IL-7R, tumor differentiation and tumor stage were the strongest predictors of survival. In addition, IL-7 upregulates MCP-1 through JAK1/STAT3 pathway to affect the migration of MDSCs and exert tumor immunosuppressive effect. Furthermore, CCR2 inhibitor and depletion of MDSCs suppressed the promoting effect of IL-7 mediated development of lung cancer. These findings provided the important mechanism that IL-7 upregulate MCP-1 through JAK1/STAT3 pathway to recruit MDSCs and put forth blockage of CCR2 inhibitor and MDSCs recruitment as a prospective immunotherapy strategy for the treatment of NSCLC.

摘要

肺癌是全球最常被诊断出的癌症之一，也是全球癌症相关死亡的主要原因。近年来，越来越多的研究表明，肿瘤免疫微环境（TIME）对肺癌的发展有重大影响。白细胞介素-7（IL-7）是适应性免疫系统的一种重要细胞因子，在不同类型的肿瘤中发挥重要的免疫调节作用。然而，IL-7与非小细胞肺癌（NSCLC）中TIME的关系尚不清楚。本研究发现，MCP-1和CD11b的表达与IL-7/IL-7R的表达相关。MCP-1、IL-7R、肿瘤分化和肿瘤分期是生存的最强预测因子。此外，IL-7通过JAK1/STAT3途径上调MCP-1，以影响骨髓来源抑制细胞（MDSCs）的迁移并发挥肿瘤免疫抑制作用。此外，CCR2抑制剂和MDSCs的耗竭抑制了IL-7介导的肺癌发展促进作用。这些发现提供了重要机制，即IL-7通过JAK1/STAT3途径上调MCP-1以募集MDSCs，并提出阻断CCR2抑制剂和MDSCs募集作为治疗NSCLC的一种前瞻性免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/9923d2e1d982/41598_2025_1868_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/6dc454a56dcb/41598_2025_1868_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/e59b46828b5d/41598_2025_1868_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/fe45ed3abfea/41598_2025_1868_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/dfc65a396ed9/41598_2025_1868_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/24f0df32c28b/41598_2025_1868_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/0a2d5132aa0b/41598_2025_1868_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/7f88ba490337/41598_2025_1868_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/9923d2e1d982/41598_2025_1868_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/6dc454a56dcb/41598_2025_1868_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/e59b46828b5d/41598_2025_1868_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/fe45ed3abfea/41598_2025_1868_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/dfc65a396ed9/41598_2025_1868_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/24f0df32c28b/41598_2025_1868_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/0a2d5132aa0b/41598_2025_1868_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/7f88ba490337/41598_2025_1868_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08d5/12081855/9923d2e1d982/41598_2025_1868_Fig8_HTML.jpg

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本文引用的文献

[1]
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[2]
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Cell Rep Med. 2024-5-21

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CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results.

Leukemia. 2024-5

[4]
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Cell Mol Immunol. 2024-5

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Lung cancer immunotherapy: progress, pitfalls, and promises.

Mol Cancer. 2023-2-21

[10]
DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity.

J Exp Med. 2022-12-5

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