Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.

中文翻译：

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影响胆道的自身免疫促进胆管癌的免疫监视


胆管癌（CCA）是胆管细胞恶性转化的结果。原发性硬化性胆管炎（PSC）和原发性胆汁性胆管炎（PBC）是胆管细胞主要受损的慢性疾病。尽管 PSC 是一种易导致 CCA 的炎症性疾病，但在 PBC 的自身免疫背景下几乎从未发现 CCA。在这里，我们假设 PBC 可能有利于 CCA 免疫监视。在用同基因 CCA 挑战的临床前小鼠胆管炎模型中，PBC（但不是 PSC）降低了 CCA 发生的频率并延迟了肿瘤生长动力学。这种与 PBC 相关的作用似乎是 CCA 特有的，因为在其他癌症（包括肝细胞癌）中没有观察到这种作用。 PBC 的保护作用依赖于 1 型和 2 型 T 细胞反应，并且在较小程度上依赖于 B 细胞。单细胞 TCR/RNA 测序揭示了 PBC 宿主的肝脏和 CCA 肿瘤之间存在共享的 TCR 克隆型。总而言之，这些结果证明胆道中自身免疫和癌症免疫监视之间存在机械重叠。