Acharya Swetha, Hegde Usha, Acharya Anirudh Balakrishna, Madhunapantula SubbaRao V, Sreeshyla Huchanahalli Sheshanna, Nitin Priyanka, Karnik Medha
Department of Oral Pathology and Microbiology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research (JSSAHER), Mysore, India.
Department of Restorative Dentistry, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Front Oral Health. 2025 Mar 24;6:1551781. doi: 10.3389/froh.2025.1551781. eCollection 2025.
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.
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.
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.
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.
https://www.crd.york.ac.uk/PROSPERO/i, identifier (CRD42023447963).
白细胞介素-33（IL-33）和肿瘤抑制因子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轴途径可能是一种有效的治疗方法。然而，IL-33/ST2表达在头颈部鳞状细胞癌（HNSCC）预后中的具体意义尚未完全明确。因此，需要更全面的研究来验证IL-33和ST2在HNSCC中的作用及临床意义。
本研究旨在评估肿瘤组织中差异表达的IL-33和ST2作为HNSCC新型生物标志物的潜力。
检索并分析了2013年1月至2023年7月期间的Web of Science、Scopus和PubMed电子数据库。
分析了9项符合纳入标准的研究。这些入选研究主要采用观察性分析研究设计，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（CAF）中表达增强。根据其中一些报告，CAF中IL-33的过表达与其在肿瘤细胞中的表达相关。CAF中IL-33水平升高与不良临床结局相关。IL-33表达增加与无淋巴结转移生存期差有关，表明HNSCC预后不良。在HNSCC中，肿瘤细胞和调节性T细胞（Treg）表达ST2。Treg上ST2的表达程度与表达IL-33的CAF的丰度相对应。IL-33增加Treg密度并增强其抑制能力。HNSCC中较差的生存结局与Treg中ST2表达升高以及表达IL-33的CAF的存在有关。
CAF驱动的癌症侵袭依赖于通过旁分泌和自分泌途径的IL-33信号传导。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轴显著影响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。
