Li Junpeng, Ozawa Yohei, Mozumi Takeru, Jiang Kaiyuan, Taniyama Yusuke, Sato Chiaki, Okamoto Hiroshi, Ishida Hirotaka, Ujiie Naoto, Ohnuma Shinobu, Unno Michiaki, Kamei Takashi
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, Japan.
Esophagus. 2025 Sep 10. doi: 10.1007/s10388-025-01152-5.
The cluster of differentiation 47 (CD47)-signal regulatory protein alpha (SIRPα) axis is a key regulator of innate immune surveillance, facilitating the neoplastic evasion of macrophage-mediated phagocytosis. Although this pathway has been implicated in tumor immune escape in multiple malignancies, its clinical and prognostic significance in esophageal squamous cell carcinoma (ESCC) remain to be fully elucidated.
We retrospectively analyzed 100 patients who underwent esophagectomy for resectable ESCC. Immunohistochemical testing determined SIRPα expression in peritumoral immune infiltrates and CD47 expression in tumor and immune cells, while tumor proportion score (TPS) and combined positive score (CPS) were used to evaluate CD47 staining. Survival outcomes and correlations with clinicopathological factors were also analyzed.
Increased expression of SIRPα, CD47 CPS, and CD47 TPS was detected in 47, 50, and 47% of patients, respectively. Elevated SIRPα expression was significantly associated with decreased overall survival. Also increased CD47 CPS and TPS was significantly associated with decreased overall survival and relapse-free survival. CD47 CPS was identified as an independent prognostic indicator for overall survival in multivariate Cox regression analysis (hazard ratio [HR] = 3.89; 95% confidence interval [CI] = 1.57-9.61; P = 0.003). Patients with concurrent high expression of both SIRPα and CD47 CPS demonstrated the poorest survival outcomes.
Overexpression of SIRPα and CD47, especially in tandem, is associated with poor clinical outcomes in ESCC, suggesting that the CD47-SIRPα axis may serve as a useful prognostic biomarker and a potential therapeutic target for newly immune checkpoint blockade in ESCC.
分化簇47（CD47）-信号调节蛋白α（SIRPα）轴是先天性免疫监视的关键调节因子，有助于肿瘤逃避巨噬细胞介导的吞噬作用。尽管该通路在多种恶性肿瘤的肿瘤免疫逃逸中发挥作用，但其在食管鳞状细胞癌（ESCC）中的临床和预后意义仍有待充分阐明。
我们回顾性分析了100例行食管切除术的可切除ESCC患者。免疫组织化学检测确定肿瘤周围免疫浸润中SIRPα的表达以及肿瘤和免疫细胞中CD47的表达，同时使用肿瘤比例评分（TPS）和联合阳性评分（CPS）评估CD47染色。还分析了生存结果及其与临床病理因素的相关性。
分别在47%、50%和47%的患者中检测到SIRPα表达增加、CD47 CPS升高和CD47 TPS升高。SIRPα表达升高与总生存期缩短显著相关。CD47 CPS和TPS升高也与总生存期和无复发生存期缩短显著相关。在多变量Cox回归分析中，CD47 CPS被确定为总生存期的独立预后指标（风险比[HR]=3.89；95%置信区间[CI]=1.57-9.61；P=0.003）。SIRPα和CD47 CPS同时高表达的患者生存结果最差。
SIRPα和CD47的过表达，尤其是同时过表达，与ESCC的不良临床结果相关，这表明CD47-SIRPα轴可能是一个有用的预后生物标志物，也是ESCC新免疫检查点阻断的潜在治疗靶点。
