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Inflammatory cells infiltrate and angiogenesis in locally advanced and metastatic cholangiocarcinoma
Author(s) -
Tamma Roberto,
Annese Tiziana,
Ruggieri Simona,
Brunetti Oronzo,
Longo Vito,
Cascardi Eliano,
Mastropasqua Mauro Giuseppe,
Maiorano Eugenio,
Silvestris Nicola,
Ribatti Domenico
Publication year - 2019
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13087
Subject(s) - cd31 , cd68 , angiogenesis , cd8 , pathology , medicine , tumor microenvironment , immune system , immunohistochemistry , inflammation , tryptase , metastasis , cancer research , cancer , mast cell , immunology
Background 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. Methods 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. Results 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. Conclusions 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.