Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy.
Medical Oncology Unit-Cancer Institute "Giovanni Paolo II", Bari, Italy.
Eur J Clin Invest. 2019 May;49(5):e13087. doi: 10.1111/eci.13087. Epub 2019 Mar 3.
Cholangiocarcinoma (CCA) is the second most common subtype of primary hepatobiliary cancer and one of the most aggressive characterized by an extremely poor prognosis with limited treatment options. Inflammatory cells in tumour microenvironment support tumour growth in term of progression, angiogenesis and metastatic capacity. A link between inflammation and biliary carcinogenesis has been previously observed but the mechanisms involved remain to be determined.
We investigated the microvascular density (MVD) and inflammatory cells in tissue samples from 40 patients with CCA with locally advanced CCA and metastatic CCA by means of immunohistochemical analysis of macrophages, mast cells, B and T lymphocytes and we correlated inflammatory infiltrate with MVD.
We observed significant decrease in the levels of CD31 positive vessels, and CD8, CD4, CD68 and tryptase-positive cells in metastatic lesions as compared to the localized ones. A negative correlation between CD31 and CD8 and CD31 and CD4 in localized CCA samples was found as assessed by Spearman correlation analysis.
In locally advanced CCA patients, there is a significant increase of immune cell infiltrate constituted by CD8 and CD4 lymphocytes, macrophages and mast cells as compared to the metastatic ones. This alteration in the tumour microenvironment infiltrate is related to a significant increased MVD in localized CCA lesions compared with the metastatic ones. Moreover, we observed a negative correlation between MVD and CD8 , CD4 cells in localized CCA patients.
胆管癌（CCA）是原发性肝胆癌的第二大亚型，也是侵袭性最强的癌症之一，其预后极差，治疗选择有限。肿瘤微环境中的炎症细胞在肿瘤的进展、血管生成和转移能力方面支持肿瘤的生长。先前已经观察到炎症与胆管癌发生之间存在联系，但涉及的机制仍有待确定。
我们通过免疫组织化学分析巨噬细胞、肥大细胞、B 和 T 淋巴细胞，研究了 40 例局部晚期和转移性 CCA 患者组织样本中的微血管密度（MVD）和炎症细胞，并将炎症浸润与 MVD 相关联。
与局限性病变相比，转移性病变中 CD31 阳性血管和 CD8、CD4、CD68 和类胰蛋白酶阳性细胞的水平显著降低。通过 Spearman 相关性分析发现，在局部 CCA 样本中，CD31 与 CD8 和 CD31 与 CD4 之间呈负相关。
与转移性病变相比，局部晚期 CCA 患者的肿瘤微环境浸润中存在显著增加的免疫细胞浸润，由 CD8 和 CD4 淋巴细胞、巨噬细胞和肥大细胞组成。与转移性病变相比，局部 CCA 病变中 MVD 的显著增加与肿瘤微环境浸润的这种改变有关。此外，我们还观察到局部 CCA 患者的 MVD 与 CD8、CD4 细胞之间存在负相关。
