Shigehara Kengo, Kawai Noriko, Shirosaki Tomohide, Ebihara Yuma, Murai Aiko, Takaya Akari, Tokita Serina, Sasaki Kenta, Shijubou Naoki, Kubo Terufumi, Murata Kenji, Kanaseki Takayuki, Tsukahara Tomohide, Hatanaka Yutaka, Mitsuhashi Tomoko, Shichinohe Toshiaki, Hirohashi Yoshihiko, Hirano Satoshi, Torigoe Toshihiko
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, 060-8556, Japan.
Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Hokkaido, 060-8648, Japan.
Sci Rep. 2025 Jul 22;15(1):26638. doi: 10.1038/s41598-025-10885-3.
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.
在许多恶性肿瘤中,肿瘤浸润淋巴细胞(TILs)数量增加被认为是一个有利的预后因素,但肾细胞癌等情况除外。然而,TIL大小的临床意义仍不明确。丝裂原激活T细胞会增加细胞大小,部分是通过c-myc表达实现的,这表明较大的T细胞可能更具活性。我们推测TIL大小可能与癌症患者的预后相关。在此,我们研究了96例食管鳞状细胞癌(ESCC)患者中肿瘤浸润性CD8 + T细胞的大小和数量与患者预后之间的关系。我们采用人工智能(AI)分析来量化每个样本中肿瘤内CD8 + T细胞的平均大小。然后根据T细胞大小的中位数将患者分为“大”和“小”CD8 + T细胞组。同样,我们根据CD8 + T细胞数量将病例分为“高”和“低”组。我们发现,单因素分析显示,大CD8 + T细胞组患者的总生存期明显优于小CD8 + T细胞组(p = 0.039),但多因素分析中差异未达到统计学意义(p = 0.054)。高CD8 + T细胞组患者的预后优于低CD8 + T细胞组。CD8 + T细胞大小与数量之间无显著相关性,它们的组合(大/高)确定了一个预后最有利的患者亚组。我们的研究结果表明,CD8 + T细胞大小可作为ESCC的独立预后标志物。