Data_Sheet_1_Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool.docx

Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 – PD-L1 –) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (p = 0.012), to either intratumoral or mixed localization of TILs (p < 0.001) and to adenocarcinoma histotype (p < 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (p = 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors.

吲哚胺2,3-双加氧酶2（Indoleamine 2,3-dioxygenase 2, IDO2）是色氨酸降解免疫调节酶吲哚胺2,3-双加氧酶1（Indoleamine 2,3-dioxygenase 1, IDO1）的同源类似物。尽管学界对IDO1的功能已有较为充分的阐释，但IDO2的具体作用仍未得到充分阐明。已有研究证实部分人类肿瘤中存在IDO2过表达现象，但IDO2表达与肿瘤进展之间的关联尚不明确，在非小细胞肺癌（Non-Small Cell Lung Cancer, NSCLC）领域尤为如此。本研究针对191例经福尔马林固定石蜡包埋的手术切除非小细胞肺癌样本，对IDO2的免疫组织化学表达水平及细胞定位进行了评估。同时分析了IDO2表达与患者临床病理特征、肿瘤浸润淋巴细胞（Tumor-Infiltrating Lymphocytes, TILs）、免疫抑制性肿瘤分子（IDO1及程序性死亡受体配体1（Programmed Cell Death Ligand-1, PD-L1））以及患者预后之间的相关性。研究结果显示，在鳞状细胞癌亚组中，IDO2高表达与PD-L1高水平呈显著正相关（p=0.012）；IDO2高表达还与肿瘤内或混合性的TILs定位（p<0.001）以及腺癌组织学类型（p<0.001）密切相关。此外，本研究检测到IDO2高表达与非小细胞肺癌患者不良预后存在显著关联（p=0.011）。本研究为非小细胞肺癌中IDO2的相关研究提供了有价值的新认知。IDO2表达与PD-L1水平升高、TILs定位特征以及非小细胞肺癌不良预后之间的紧密关联，提示IDO2可作为潜在的预后生物标志物，为优化免疫检查点抑制剂联合创新治疗方案提供了可行方向。