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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10885-3
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Summary: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.
ISSN:2045-2322