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IF 3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Frontiers in oral health Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI:10.3389/froh.2025.1551781

Swetha Acharya, Usha Hegde, Anirudh Balakrishna Acharya, SubbaRao V Madhunapantula, Huchanahalli Sheshanna Sreeshyla, Priyanka Nitin, Medha Karnik

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摘要

背景：白细胞介素-33（IL-33）和致瘤抑制因子 2（ST2）的表达与多种癌症的肿瘤生长和进展密切相关，这表明靶向 IL-33/ST2 轴通路可能是一种有利的治疗方法。然而，IL-33/ST2 的表达对头颈部鳞状细胞癌（HNSCC）预后的具体影响尚不完全清楚。因此，需要更全面的研究来验证 IL-33 和 ST2 在 HNSCC 中的任务和临床意义：本研究旨在评估肿瘤组织中差异表达的 IL-33 和 ST2 作为 HNSCC 新型生物标记物的潜力：对2013年1月至2023年7月期间的Web of Science、Scopus和PubMed电子数据库进行了检索和分析：对符合纳入标准的 9 项研究进行了分析。这些入选研究主要采用观察分析研究设计，主要在东南亚人群中进行。IL-33 主要位于基质中，在癌相关成纤维细胞（CAFs）中的表达增强。IL-33在CAFs中的过表达与其在肿瘤细胞中的表达相关，这与其中一些报道相符。CAFs中IL-33水平的升高与不利的临床结果有关。IL-33 表达增加与无结节转移生存率低有关，表明 HNSCC 预后不良。在 HNSCC 中，肿瘤细胞和调节性 T 细胞（Tregs）表达 ST2。Tregs表达ST2的程度与表达IL-33的CAFs的丰度相对应。IL-33 增加了 Tregs 的密度，并增强了它们的抑制能力。HNSCC较差的生存结果与Tregs中ST2表达的升高以及表达IL-33的CAFs的存在有关：结论：CAF驱动的癌症侵袭性依赖于IL-33通过旁分泌和自分泌途径发出的信号。IL-33可能是一种预后生物标志物和治疗靶点，旨在改善HNSCC的预后和生存率。IL-33/ST2轴显著配置了HNSCC的肿瘤微环境和肿瘤侵袭性。血清IL33和ST2在HNSCC中的作用仍有待进一步研究。系统综述注册：https://www.crd.york.ac.uk/PROSPERO/i，标识符（CRD42023447963）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Prognostic significance of IL-33 and ST2 expression in head and neck squamous cell carcinoma: a systematic review.

Background: Interleukin-33 (IL-33) and Suppression of tumorigenicity 2 (ST2) expression are strongly associated with tumor growth and progression in diverse cancers, indicating the possibility of targeting the IL-33/ST2 axis pathway as a favorable therapeutic approach. However, the specific implications of IL-33/ST2 expression in Head and Neck Squamous Cell Carcinoma (HNSCC) prognosis are not fully understood. Thus, there is a need for more comprehensive research to verify the tasks and clinical significance of IL-33 and ST2 in HNSCC.

Objectives: The objective of this study was to evaluate the potential of differentially expressed IL-33 and ST2 in tumor tissues that could serve as novel biomarkers in HNSCC.

Material & methods: The Web of Science, Scopus, and PubMed electronic databases were searched and analyzed from January 2013 to July 2023.

Results: Nine studies fulfilling the inclusion criteria were analyzed. These selected studies were mainly having observational analytical study design, predominantly conducted within the Southeast Asian population. IL-33, primarily located in the stroma, demonstrates enhanced expression within carcinoma-associated fibroblasts (CAFs). Overexpression of IL-33 in CAFs correlates with its expression in tumor cells, as per some of these reports. Elevated IL-33 levels in CAFs are associated with unfavorable clinical outcomes. Increased IL-33 expression is related to poor nodal metastasis-free survival, indicating an adverse prognosis in HNSCC. In HNSCC, tumor cells and regulatory T cells (Tregs) expressed ST2. The degree of ST2 expression on Tregs corresponds to the abundance of IL-33 expressing CAFs. IL-33 increases the Tregs density and amplifies their suppressive capability. Poorer survival outcomes in HNSCC are linked to elevated ST2 expression in Tregs combined with the existence of IL-33-expressing CAFs.

Conclusion: CAF-driven cancer invasiveness relies on IL-33 signaling via paracrine and autocrine pathways. IL-33 may be a prognostic biomarker and therapeutic target, aiming to improve prognosis and survival in HNSCC. The IL-33/ST2 axis significantly configures the tumor microenvironment and tumor aggressiveness in HNSCC. The role of serum IL33 and ST2 remains to be further studied in HNSCC.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/i, identifier (CRD42023447963).

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