von Bubnoff Dagmar, Schmitt Christina, Goldinger Simone M, Schadendorf Dirk, Kähler Katharina C, Hafner Christian, Kramer Nora, Fröhlich Waltraud, Dummer Reinhard, Berking Carola, Schliep Stefan, Kirchberger Michael C, Heinzerling Lucie
Department of Dermatology, University Hospital Lübeck, Lübeck, Germany.
Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany.
PLoS One. 2025 May 7;20(5):e0321937. doi: 10.1371/journal.pone.0321937. eCollection 2025.
The tumor microenvironment is crucial for prognosis and response to immunotherapy in several tumor entities.
In a multicenter retrospective study, a total of 86 tumor samples from patients with metastatic melanoma were evaluated for baseline expression of indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PD-L1). Expression patterns of IDO and PD-L1 on tumor cells and antigen-presenting cells (APCs) as determined by immunohistochemical (IHC) staining of paraffin-embedded tissue sections were correlated with response to ipilimumab and overall survival (OS). Statistical analysis was performed using the Spearman correlation, the Mann-Whitney test and Kaplan-Meier estimator.
IDO expression in tumor cells or APCs was not predictive for treatment response. The median OS was 26 months in IDO-positive and IDO-negative patients, regardless of IDO expression in tumor cells or APCs. A correlation of IHC expression scores of IDO and PD-L1 could not be documented.
The exact role of IDO in creating an immunosuppressive tumor environment and its reversal needs to be further elucidated.
肿瘤微环境对多种肿瘤实体的预后及免疫治疗反应至关重要。
在一项多中心回顾性研究中,对86例转移性黑色素瘤患者的肿瘤样本进行评估,检测吲哚胺2,3-双加氧酶(IDO)和程序性死亡配体1(PD-L1)的基线表达。通过对石蜡包埋组织切片进行免疫组织化学(IHC)染色,确定IDO和PD-L1在肿瘤细胞及抗原呈递细胞(APC)上的表达模式,并将其与伊匹单抗治疗反应及总生存期(OS)相关联。采用Spearman相关性分析、Mann-Whitney检验及Kaplan-Meier估计法进行统计分析。
肿瘤细胞或APC中IDO的表达不能预测治疗反应。无论肿瘤细胞或APC中IDO的表达情况如何,IDO阳性和IDO阴性患者的中位OS均为26个月。未发现IDO和PD-L1的IHC表达评分之间存在相关性。
IDO在创建免疫抑制性肿瘤环境中的确切作用及其逆转机制有待进一步阐明。