Supplementary Material for: Prognostic role of PD-L1 and IDO-1 expression in sinonasal carcinoma

Introduction: Sinonasal carcinomas (SNC) are rare, aggressive tumours with complex immunological aspects. Still, prognostic markers are missing. The study aimed to investigate the relationship between immune checkpoints - specifically programmed death-ligand 1 (PD-L1) and Indolamin-2,3-dioxygenase 1 (IDO-1) - and clinical parameters in SNC.
Methods: In this monocentric study immunohistochemical analysis of the checkpoints PD-L1 and IDO-1 was carried out in 85 SNC patients from 2004 to 2020. Tumour proportion score (TPS), combined positive score (CPS) and combined IDO-1 score classified the PD-L1 and IDO-1 expression. The study was conducted in a specialized tertiary care center, indicating comprehensive multidisciplinary care with surgical, radiotherapeutic and systemic treatment intervention.
Results: Over a median observation period of 41 months, 52 squamous cell carcinomas (SCC, 61%) and 33 adenocarcinomas (AC, 39%) were included. 31 patients (37%) were classified in UICC IV stage, 90.6 % (n=77) received a primary resection. 3-year progression-free survival (PFS)/-overall survival (OS) rates were 63.6% / 81.4% in SCC and 73.1% / 82.5% in AC, respectively. Sinonasal AC showed significantly more frequently negative PD-L1 expression and CPS <1 compared to sinonasal SCC (p=0.035, p=0.002). Sinonasal SCC with TPS Score >50%, combined low IDO-1 Score and high UICC stage showed significantly worse 3-year-PFS and – OS values (p<0.05).
Conclusion: The study identifies PD-L1 and IDO-1 as possible prognostic factors for sinonasal SCC, but less so for sinonasal AC. A TPS Score >50% and combined low IDO-1 score correlate with shortened 3-year-PFS and -OS in sinonasal SCC. Immune checkpoints could therefore represent important target molecules for the prognosis assessment of sinonasal SCC.

引言：鼻窦癌（Sinonasal Carcinomas, SNC）是一类罕见的侵袭性肿瘤，其免疫学特征复杂，目前仍缺乏有效的预后标志物。本研究旨在探讨免疫检查点（immune checkpoints）——尤其是程序性死亡配体1（programmed death-ligand 1, PD-L1）与吲哚胺2,3-双加氧酶1（Indolamin-2,3-dioxygenase 1, IDO-1）——与鼻窦癌临床参数之间的关联。

方法：本研究为单中心研究，纳入2004年至2020年间的85例鼻窦癌患者，对其PD-L1与IDO-1免疫检查点进行免疫组化分析。采用肿瘤比例评分（Tumour Proportion Score, TPS）、联合阳性评分（Combined Positive Score, CPS）以及联合IDO-1评分对PD-L1和IDO-1的表达水平进行分级。本研究在一家专业三级医疗中心开展，该中心可提供涵盖手术、放疗及系统性治疗的多学科综合诊疗服务。

结果：中位随访时间为41个月，本研究共纳入52例鳞状细胞癌（Squamous Cell Carcinoma, SCC，占比61%）与33例腺癌（Adenocarcinoma, AC，占比39%）。其中31例患者（37%）分期为国际抗癌联盟（Union for International Cancer Control, UICC）IV期，90.6%（n=77）的患者接受了原发灶切除术。鳞状细胞癌组的3年无进展生存期（Progression-Free Survival, PFS）与总生存期（Overall Survival, OS）率分别为63.6%与81.4%，腺癌组则分别为73.1%与82.5%。与鼻窦鳞状细胞癌相比，鼻窦腺癌的PD-L1阴性表达率与CPS<1的比例显著更高（p=0.035，p=0.002）。TPS评分>50%、联合IDO-1低评分且UICC分期较高的鼻窦鳞状细胞癌患者，其3年无进展生存期与总生存期均显著更差（p<0.05）。

结论：本研究证实PD-L1与IDO-1可作为鼻窦鳞状细胞癌的潜在预后因子，但对鼻窦腺癌的预后预测价值有限。在鼻窦鳞状细胞癌患者中，TPS评分>50%且联合IDO-1低评分与更短的3年无进展生存期及总生存期相关。因此，免疫检查点可作为鼻窦鳞状细胞癌预后评估的重要靶标分子。