Tryptophan catabolism is used by tumors to resist immune attack. It can be catalyzed by indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO). IDO1 is frequently expressed in tumors and has been widely studied as a potential therapeutic target to reduce resistance to cancer immunotherapy. In contrast, TDO expression in tumors is not well characterized. Several human tumor cell lines constitutively express enzymatically active TDO. In human tumor samples, TDO expression has previously been detected by transcriptomics, but the lack of validated antibodies has precluded detection of the TDO protein and identification of TDO-expressing cells. Here, we developed novel TDO-specific monoclonal antibodies and confirmed by immunohistochemistry the expression of TDO in the majority of human cancers. In all hepatocarcinomas (10/10), TDO was expressed by most tumor cells. Some glioblastomas (10/39) and kidney carcinomas (1/10) also expressed TDO in tumor cells themselves but only in focal tumor areas. In addition, all cancers tested contained foci of nontumoral TDO-expressing cells, which were identified as pericytes by their expression of PDGFRβ and their location in vascular structures. These TDO-expressing pericytes belonged to morphologically abnormal tumor vessels and were found in high-grade tumors in the vicinity of necrotic or hemorrhagic areas, which were characterized by neoangiogenesis. We observed similar TDO-expressing pericytes in inflammatory pulmonary lesions containing granulation tissue, and in chorionic villi, two tissue types that also feature neoangiogenesis. Our results confirm TDO as a relevant immunotherapeutic target in hepatocellular carcinoma and suggest a proangiogenic role of TDO in other cancer types.See article by Schramme et al., p. 32.

中文翻译：

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色氨酸2，3-双加氧酶表达在人类肝癌细胞和大多数癌症的瘤内周细胞中被鉴定。

色氨酸分解代谢被肿瘤用于抵抗免疫攻击。吲哚胺2,3-双加氧酶（IDO1）和色氨酸2,3-双加氧酶（TDO）可以催化它。IDO1常在肿瘤中表达，并且已被广泛研究为降低癌症免疫疗法耐药性的潜在治疗靶标。相反，TDO在肿瘤中的表达没有得到很好的表征。几种人肿瘤细胞系组成性表达酶活性的TDO。在人类肿瘤样品中，TDO表达先前已通过转录组学进行了检测，但是缺乏经过验证的抗体已无法检测TDO蛋白和鉴定表达TDO的细胞。在这里，我们开发了新颖的TDO特异性单克隆抗体，并通过免疫组织化学证实了TDO在大多数人类癌症中的表达。在所有肝癌（10/10）中，大多数肿瘤细胞表达TDO。一些胶质母细胞瘤（10/39）和肾癌（1/10）在肿瘤细胞本身也表达TDO，但仅在局灶性肿瘤区域表达。此外，所有测试的癌症均包含非肿瘤TDO表达细胞灶，通过其PDGFRβ的表达及其在血管结构中的位置将其鉴定为周细胞。这些表达TDO的周细胞属于形态异常的肿瘤血管，并且在坏死或出血区域附近的高级肿瘤中发现，其特征在于新血管生成。我们在包含肉芽组织的炎性肺部病变和绒毛膜绒毛中观察到了类似的表达TDO的周细胞，这两种组织类型也具有新生血管生成的特征。我们的结果证实了TDO是肝细胞癌的相关免疫治疗靶标，并暗示了TDO在其他癌症类型中的促血管生成作用。32。