The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma
Abstract In many malignancies, an increased number of tumor-infiltrating lymphocytes (TILs) is recognized as a favorable prognostic factor, with exceptions such as renal cell carcinoma. However, the clinical significance of TIL size remains unclear. T-cell activation by mitogens increases cell size,...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-10885-3 |
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| author | Kengo Shigehara Noriko Kawai Tomohide Shirosaki Yuma Ebihara Aiko Murai Akari Takaya Serina Tokita Kenta Sasaki Naoki Shijubou Terufumi Kubo Kenji Murata Takayuki Kanaseki Tomohide Tsukahara Yutaka Hatanaka Tomoko Mitsuhashi Toshiaki Shichinohe Yoshihiko Hirohashi Satoshi Hirano Toshihiko Torigoe |
| author_facet | Kengo Shigehara Noriko Kawai Tomohide Shirosaki Yuma Ebihara Aiko Murai Akari Takaya Serina Tokita Kenta Sasaki Naoki Shijubou Terufumi Kubo Kenji Murata Takayuki Kanaseki Tomohide Tsukahara Yutaka Hatanaka Tomoko Mitsuhashi Toshiaki Shichinohe Yoshihiko Hirohashi Satoshi Hirano Toshihiko Torigoe |
| author_sort | Kengo Shigehara |
| collection | DOAJ |
| description | Abstract In many malignancies, an increased number of tumor-infiltrating lymphocytes (TILs) is recognized as a favorable prognostic factor, with exceptions such as renal cell carcinoma. However, the clinical significance of TIL size remains unclear. T-cell activation by mitogens increases cell size, partly via c-myc expression, suggesting that larger T cells may be more activated. We hypothesized that TIL size might be prognostically relevant in cancer patients. Here, we examined the relationship between the size and number of tumor-infiltrating CD8 + T cells and patient prognosis in 96 cases of esophageal squamous cell carcinoma (ESCC). We employed artificial intelligence (AI) analysis to quantify the mean size of intratumoral CD8+ T cells in each sample. Patients were then divided into “Large” and “Small” CD8+ T cell groups according to the median T-cell size. Similarly, we classified cases into “High” and “Low” groups based on CD8 + T-cell numbers. We found that patients in the Large CD8+ T cell group had significantly better overall survival than those in the Small CD8+ T cell group by a univariate analysis (p = 0.039), but the difference did not reach statistical significance in a multivariate analysis (p = 0.054). Patients in the High CD8 + T cell group had better outcomes than those in the Low CD8+ T cell group. There was no significant correlation between CD8+ T cell size and count, and their combination (Large/High) identified a subgroup of patients with the most favorable prognosis. Our findings suggest that CD8+ T cell size could serve as an independent prognostic marker in ESCC. |
| format | Article |
| id | doaj-art-d4b39ed4abed48bc89ea18dd357c1468 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d4b39ed4abed48bc89ea18dd357c14682025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-10885-3The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinomaKengo Shigehara0Noriko Kawai1Tomohide Shirosaki2Yuma Ebihara3Aiko Murai4Akari Takaya5Serina Tokita6Kenta Sasaki7Naoki Shijubou8Terufumi Kubo9Kenji Murata10Takayuki Kanaseki11Tomohide Tsukahara12Yutaka Hatanaka13Tomoko Mitsuhashi14Toshiaki Shichinohe15Yoshihiko Hirohashi16Satoshi Hirano17Toshihiko Torigoe18Department of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Gastroenterological Surgery II, Hokkaido University Faculty of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineCenter for Development of Advanced Diagnostics (C-DAD)Department of Surgical Pathology, Hokkaido University HospitalDepartment of Gastroenterological Surgery II, Hokkaido University Faculty of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineDepartment of Gastroenterological Surgery II, Hokkaido University Faculty of MedicineDepartment of Pathology, Sapporo Medical University School of MedicineAbstract In many malignancies, an increased number of tumor-infiltrating lymphocytes (TILs) is recognized as a favorable prognostic factor, with exceptions such as renal cell carcinoma. However, the clinical significance of TIL size remains unclear. T-cell activation by mitogens increases cell size, partly via c-myc expression, suggesting that larger T cells may be more activated. We hypothesized that TIL size might be prognostically relevant in cancer patients. Here, we examined the relationship between the size and number of tumor-infiltrating CD8 + T cells and patient prognosis in 96 cases of esophageal squamous cell carcinoma (ESCC). We employed artificial intelligence (AI) analysis to quantify the mean size of intratumoral CD8+ T cells in each sample. Patients were then divided into “Large” and “Small” CD8+ T cell groups according to the median T-cell size. Similarly, we classified cases into “High” and “Low” groups based on CD8 + T-cell numbers. We found that patients in the Large CD8+ T cell group had significantly better overall survival than those in the Small CD8+ T cell group by a univariate analysis (p = 0.039), but the difference did not reach statistical significance in a multivariate analysis (p = 0.054). Patients in the High CD8 + T cell group had better outcomes than those in the Low CD8+ T cell group. There was no significant correlation between CD8+ T cell size and count, and their combination (Large/High) identified a subgroup of patients with the most favorable prognosis. Our findings suggest that CD8+ T cell size could serve as an independent prognostic marker in ESCC.https://doi.org/10.1038/s41598-025-10885-3Esophageal squamous cell carcinomaTumor-infiltrating lymphocytesCD8Lymphocyte size |
| spellingShingle | Kengo Shigehara Noriko Kawai Tomohide Shirosaki Yuma Ebihara Aiko Murai Akari Takaya Serina Tokita Kenta Sasaki Naoki Shijubou Terufumi Kubo Kenji Murata Takayuki Kanaseki Tomohide Tsukahara Yutaka Hatanaka Tomoko Mitsuhashi Toshiaki Shichinohe Yoshihiko Hirohashi Satoshi Hirano Toshihiko Torigoe The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma Scientific Reports Esophageal squamous cell carcinoma Tumor-infiltrating lymphocytes CD8 Lymphocyte size |
| title | The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma |
| title_full | The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma |
| title_fullStr | The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma |
| title_full_unstemmed | The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma |
| title_short | The size of CD8+ infiltrating T cells is a prognostic marker for esophageal squamous cell carcinoma |
| title_sort | size of cd8 infiltrating t cells is a prognostic marker for esophageal squamous cell carcinoma |
| topic | Esophageal squamous cell carcinoma Tumor-infiltrating lymphocytes CD8 Lymphocyte size |
| url | https://doi.org/10.1038/s41598-025-10885-3 |
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