Haiyan Guo, Chun Liu, Kun Wu, Yan Li, Zhen Zhang, Fuxiang Chen
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引用次数: 0
摘要
调节性T细胞（Regulatory T cells, Tregs）在多种癌症类型的肿瘤微环境（tumor microenvironment， TME）中发挥免疫抑制作用。然而，不同Treg亚群对头颈部鳞状细胞癌（HNSCC）的影响和作用尚不清楚。通过单细胞RNA测序（scRNA-seq），我们发现了一个促进HNSCC进展的IL1R2+Treg亚群。通过组织微分析（TMA）和酶联免疫吸附试验（ELISA）验证了IL1R2+Treg和可溶性IL1R2 （sIL1R2）的临床诊断价值。此外，我们构建荷瘤小鼠模型，探讨联合靶向IL1R2和CTLA4的抗肿瘤作用。在机制上，我们发现IL-1β促进Tregs中IL1R2和CTLA4的表达，并通过NR4A1易位上调CTLA4。这些结果表明，IL1R2+Treg和血清IL1R2水平对HNSCC具有潜在的诊断和预后价值，联合靶向IL1R2和CTLA4可能是抑制肿瘤进展的有效策略。
Single-cell RNA sequencing reveals an IL1R2+Treg subset driving immunosuppressive microenvironment in HNSCC.
Regulatory T cells (Tregs) play an immunosuppressive role in tumor microenvironment (TME) in various of cancer types. However, how different Treg subsets influence and effect on head and neck squamous cell carcinoma (HNSCC) remain unclear. Here, using single-cell RNA sequencing (scRNA-seq), we identified an IL1R2+Treg subset which promoted the progression of HNSCC. Via tissue microassay (TMA) and enzyme-linked immunosorbent assay (ELISA), we verified the clinical diagnostic value of the IL1R2+Treg and soluble IL1R2 (sIL1R2). In addition, we constructed tumor-bearing mouse models to explore the antitumor effects of combined targeting IL1R2 and CTLA4. For mechanism, we found IL-1β promoted the expression of IL1R2 and CTLA4 in Tregs, and upregulated CTLA4 though NR4A1 translocation. These results revealed that IL1R2+Treg and serum IL1R2 level had potential diagnostic and prognostic value of HNSCC and combined targeting of IL1R2 and CTLA4 might be an effective strategy to inhibit tumor progression.
期刊介绍：
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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