Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
Hum Pathol. 2018 May;75:81-90. doi: 10.1016/j.humpath.2018.02.004. Epub 2018 Feb 13.
Programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO) are both immunosuppressive proteins. Here, we investigated the relationship between PD-1 and IDO in the tumor microenvironment (TME) and in tumor-draining lymph nodes (TDLNs) in breast cancer patients. First, the protein and mRNA expression levels of PD-1 and IDO in 20 frozen tissues were examined using Western blotting and real-time polymerase chain reaction. Second, 151 paraffin-embedded breast samples and 52 lymph node samples were analyzed by immunohistochemistry. Third, correlation and survival data for PD-1 and IDO in 963 breast tumor patients were mined using the cBio Cancer Genomics Portal. We found that the protein expression level of IDO was significantly increased in frozen tumor tissues (P = .005). From paraffin-embedded samples in the TME, PD-1 cells were only located in the stroma, while IDO was expressed in myoepithelial, stromal, and tumor cells. PD-1 and stromal IDO in the TME showed increased expression in tumors (P< .001 and P < .001, respectively). In TDLNs, PD-1 cells were primarily located in the germinal centers (GCs), and IDO cells were primarily located in the paracortex. Normal lymph nodes expressed PD-1 and IDO at the same level as non-metastatic and metastatic lymph nodes (P = .151 and P = .812, respectively). According to cBioPortal, the correlation analysis showed that IDO and PD-1 had high correlation coefficients (r = 0.83). These findings suggest that there is a positive correlation between the expression of PD-1 and IDO and that blocking both PD-1 and IDO pathways may represent an attractive therapeutic strategy in breast cancer treatment.
程序性细胞死亡蛋白 1（PD-1）和吲哚胺 2,3-双加氧酶（IDO）都是免疫抑制蛋白。在这里，我们研究了乳腺癌患者肿瘤微环境（TME）和肿瘤引流淋巴结（TDLNs）中 PD-1 和 IDO 之间的关系。首先，使用 Western blot 和实时聚合酶链反应检测 20 个冷冻组织中 PD-1 和 IDO 的蛋白和 mRNA 表达水平。其次，通过免疫组织化学分析了 151 个石蜡包埋的乳腺样本和 52 个淋巴结样本。第三，使用 cBio Cancer Genomics Portal 挖掘了 963 名乳腺癌患者 PD-1 和 IDO 的相关性和生存数据。我们发现 IDO 的蛋白表达水平在冷冻肿瘤组织中显着增加（P =.005）。从 TME 的石蜡包埋样本来看，PD-1 细胞仅位于基质中，而 IDO 则在肌上皮细胞、基质和肿瘤细胞中表达。TME 中的 PD-1 和基质 IDO 在肿瘤中表达增加（P<.001 和 P <.001）。在 TDLNs 中，PD-1 细胞主要位于生发中心（GCs），IDO 细胞主要位于副皮质区。正常淋巴结的 PD-1 和 IDO 表达水平与非转移性和转移性淋巴结相同（P =.151 和 P =.812）。根据 cBioPortal，相关性分析表明 IDO 和 PD-1 具有高相关系数（r = 0.83）。这些发现表明 PD-1 和 IDO 的表达之间存在正相关，阻断 PD-1 和 IDO 两条途径可能代表一种有吸引力的乳腺癌治疗策略。
