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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 |
doi: 10.3389/fcell.2025.1502073
This article is part of the Research Topic Molecular Mechanisms and Therapeutic Strategies of Head and Neck Disease View all articles
The Immunological Landscape of CCL26 High Invasive Oral Squamous Cell Carcinoma
Provisionally accepted
Lingyun Liu 1,2
Shuo Guan 1,2
Yizhuo Xue 1,2* Yijia He 1,2*
Liang Ding 1,2 Yong Fu 1,2* Sheng Chen 2* Zhiyong Wang 2* Yi Wang 1,2*- 1 Nanjing University, Nanjing, China
- 2 Nanjing Stomatological Hospital, Medical School of Nanjing University., Nanjing, Liaoning Province, China
Background: Our previous study demonstrated that CCL26 secreted by cancer-associated fibroblasts (CAF) promoted the invasive phenotype of oral squamous cell carcinoma (OSCC), however, more comprehensive clinical expression patterns of CCL26 and its role in immunotherapy remains ambiguous. Methods: CCL26 levels in different cancer and normal tissues were analyzed and validated in 67 OSCC patients through immunohistochemical staining (IHC). The clinical spatial distribution pattern of CCL26 in tumor microenvironment was determined, and its clinical outcomes were investigated. We also determined the invasive phenotype of tumor cells with distinct CCL26 level and explored its immune checkpoint and immunocytes relevance by differentially expressed gene (DEG) analysis, GSEA, and GO analysis. We collected peripheral blood from 28 OSCC patients to assess the percentage and absolute number of lymphocytes by flow cytometry. Results: CCL26 was upregulated in HNSC and preferentially high-expressed on CAFs and tumor cells in OSCC patients, which exhibits a trend toward decreased overall survival. CCL26high OSCC had a characteristic of tumor invasive phenotype with upregulated CLDN8/20 and reduced keratin KRT36, which was significantly associated with EMT markers (CDH1, CDH2, VIM, SNAI2). In addition, CCL26high OSCC was found to be associated with immunoglobulin mediated immune response, B cell mediated immunity et al. Indeed, immune checkpoint molecules (PD-L1, PD-L2, et al.) also decreased in CCL26high OSCC. However, CCL26 did not affect T/B/NK lymphocytes in peripheral blood of OSCC patients. Conclusion: CCL26 could regulate Immune balance and promote invasiveness of OSCC, which gave a new insight into a potential immunotherapy strategy.
Keywords: OSCC, CCL26, Survival prognosis model, immune cell, Immune check points, Immunotherapy
Received: 26 Sep 2024; Accepted: 08 Jan 2025.
Copyright: © 2025 Liu, Guan, Xue, He, Ding, Fu, Chen, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yizhuo Xue, Nanjing University, Nanjing, China
Yijia He, Nanjing University, Nanjing, China
Yong Fu, Nanjing University, Nanjing, China
Sheng Chen, Nanjing Stomatological Hospital, Medical School of Nanjing University., Nanjing, Liaoning Province, China
Zhiyong Wang, Nanjing Stomatological Hospital, Medical School of Nanjing University., Nanjing, Liaoning Province, China
Yi Wang, Nanjing Stomatological Hospital, Medical School of Nanjing University., Nanjing, Liaoning Province, China
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