Konishi Hirona, Urabe Yuji, Hatsushika Yoshiki, Masuda Satoshi, Nakamura Takeo, Ishibashi Kazuki, Mizuno Junichi, Takasago Takeshi, Tanaka Hidenori, Tsuboi Akiyoshi, Yamashita Ken, Hiyama Yuichi, Kishida Yoshihiro, Takigawa Hidehiko, Ishikawa Akira, Kuwai Toshio, Hamai Yoichi, Murakami Yuji, Oka Shiro
Department of Gastroenterology, Hiroshima University Hospital, 1-2-3, Kasumi, Minamiku, Hiroshima, 734-8551, Japan.
Department of Clinical Research Center, Hiroshima University Hospital, Hiroshima, Japan.
J Gastroenterol. 2025 Jul 25. doi: 10.1007/s00535-025-02286-0.
Various subtypes of tumor-infiltrating lymphocytes (TILs) are associated with prognosis in various cancer types. In esophageal squamous cell carcinoma (ESCC), TILs have been associated with prognosis in advanced stages of the disease. However, their significance in superficial esophageal squamous cell carcinoma (SESCC) remains unknown. In this study, we investigated the role of TILs in SESCC.
First, we included 212 SESCC lesions with a diameter of 10-20 mm (65 pT1a-EP, 74 pT1a-LPM,40 pT1a-MM, and 33 pT1b-SM lesions) that were resected at our hospital from November 2007 to December 2019. We then examined changes in TILs related to tumor invasion. We evaluated the phenotype and number of TILs using triple immunofluorescence staining for CD4, CD8, and FoxP3. In addition, we selected 97 consecutive pT1b-SM lesions treated during the same period. These specimens were used to examine the association between TILs and lymph node metastasis (LNM) in pT1b-SM cases.
The number of CD4 + , CD8 + , and FoxP3 + TILs infiltrating the tumor increased significantly with increasing invasion depth. In pT1b-SM lesions, CD4 + , CD8 + , and FoxP3 + TIL counts were significantly higher in the invasive front (IF) than in the tumor center (CT). Moreover, in patients undergoing surgical resection or endoscopic submucosal dissection (regardless of additional chemoradiotherapy), the number and ratio of FoxP3 + TILs in IF were significantly higher in patients with LNM than in those without, suggesting their potential utility as predictive biomarkers.
The number and ratio of FoxP3 + TILs in the IF may be an indicator of LNM risk in SESCC.
多种肿瘤浸润淋巴细胞（TILs）亚型与多种癌症类型的预后相关。在食管鳞状细胞癌（ESCC）中，TILs与疾病晚期的预后相关。然而，它们在浅表食管鳞状细胞癌（SESCC）中的意义仍不清楚。在本研究中，我们调查了TILs在SESCC中的作用。
首先，我们纳入了2007年11月至2019年12月在我院切除的212个直径为10 - 20毫米的SESCC病变（65个pT1a-EP、74个pT1a-LPM、40个pT1a-MM和33个pT1b-SM病变）。然后，我们检查了与肿瘤浸润相关的TILs变化。我们使用针对CD4、CD8和FoxP3的三重免疫荧光染色评估TILs的表型和数量。此外，我们选择了同期治疗的97个连续的pT1b-SM病变。这些标本用于检查pT1b-SM病例中TILs与淋巴结转移（LNM）之间的关联。
随着浸润深度的增加，浸润肿瘤的CD4 +、CD8 +和FoxP3 + TILs数量显著增加。在pT1b-SM病变中，侵袭前沿（IF）的CD4 +、CD8 +和FoxP3 + TIL计数显著高于肿瘤中心（CT）。此外，在接受手术切除或内镜黏膜下剥离术的患者中（无论是否进行额外的放化疗），发生LNM的患者IF中FoxP3 + TILs的数量和比例显著高于未发生LNM的患者，表明它们作为预测生物标志物的潜在效用。
IF中FoxP3 + TILs的数量和比例可能是SESCC中LNM风险的一个指标。
