The immunological landscape of CCL26High invasive oral squamous cell carcinoma
BackgroundOur 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.MethodsCCL26...
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Frontiers Media S.A.
2025-01-01
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author | Lingyun Liu Lingyun Liu Shuo Guan Shuo Guan Yizhuo Xue Yizhuo Xue Yijia He Yijia He Liang Ding Yong Fu Sheng Chen Zhiyong Wang Yi Wang |
author_facet | Lingyun Liu Lingyun Liu Shuo Guan Shuo Guan Yizhuo Xue Yizhuo Xue Yijia He Yijia He Liang Ding Yong Fu Sheng Chen Zhiyong Wang Yi Wang |
author_sort | Lingyun Liu |
collection | DOAJ |
description | BackgroundOur 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.MethodsCCL26 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.ResultsCCL26 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.ConclusionCCL26 could regulate Immune balance and promote invasiveness of OSCC, which gave a new insight into a potential immunotherapy strategy. |
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language | English |
publishDate | 2025-01-01 |
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spelling | doaj-art-7b0973d0df8146b7abac1dba169881de2025-01-27T06:40:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15020731502073The immunological landscape of CCL26High invasive oral squamous cell carcinomaLingyun Liu0Lingyun Liu1Shuo Guan2Shuo Guan3Yizhuo Xue4Yizhuo Xue5Yijia He6Yijia He7Liang Ding8Yong Fu9Sheng Chen10Zhiyong Wang11Yi Wang12Central Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, ChinaCentral Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, ChinaCentral Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, ChinaCentral Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, ChinaCentral Laboratory of Stomatology, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaDepartment of Oral Pathology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical School, Nanjing Stomatological Hospital, Nanjing University, Nanjing, ChinaBackgroundOur 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.MethodsCCL26 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.ResultsCCL26 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.ConclusionCCL26 could regulate Immune balance and promote invasiveness of OSCC, which gave a new insight into a potential immunotherapy strategy.https://www.frontiersin.org/articles/10.3389/fcell.2025.1502073/fullOSCCCCL26survival prognosis modelimmune cellimmune check pointsimmunotherapy |
spellingShingle | Lingyun Liu Lingyun Liu Shuo Guan Shuo Guan Yizhuo Xue Yizhuo Xue Yijia He Yijia He Liang Ding Yong Fu Sheng Chen Zhiyong Wang Yi Wang The immunological landscape of CCL26High invasive oral squamous cell carcinoma Frontiers in Cell and Developmental Biology OSCC CCL26 survival prognosis model immune cell immune check points immunotherapy |
title | The immunological landscape of CCL26High invasive oral squamous cell carcinoma |
title_full | The immunological landscape of CCL26High invasive oral squamous cell carcinoma |
title_fullStr | The immunological landscape of CCL26High invasive oral squamous cell carcinoma |
title_full_unstemmed | The immunological landscape of CCL26High invasive oral squamous cell carcinoma |
title_short | The immunological landscape of CCL26High invasive oral squamous cell carcinoma |
title_sort | immunological landscape of ccl26high invasive oral squamous cell carcinoma |
topic | OSCC CCL26 survival prognosis model immune cell immune check points immunotherapy |
url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1502073/full |
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