Intrahepatic cholangiocarcinoma (iCCA) represents a heterogeneous group of malignancies emerging from the biliary tree, often in the context of chronic bile ducts inflammation. The immunological features of iCCA cells and their capability to control the lymphocytes response have not yet been investigated. The aims of the present study were to evaluate the interaction between iCCA cells and human peripheral blood mononuclear cells (PBMCs) and the role of Fas/FasL in modulating T-cells and NK-cells response after direct co-culture. iCCA cells express high levels of Fas and FasL that increase after co-culture with PBMCs inducing apoptosis in CD4(+), CD8(+) T-cells and in CD56(+) NK-cells. In vitro, c-FLIP is expressed in iCCA cells and the co-culture with PBMCs induces an increase of c-FLIP in both iCCA cells and biliary tree stem cells. This c-FLIP increase does not trigger the caspase cascade, thus hindering apoptotis of iCCA cells which, instead, underwent proliferation. The increased expression of Fas, FasL and c-FLIP is confirmed in situ, in human CCA and in primary sclerosing cholangitis. In conclusion our data indicated that iCCA cells have immune-modulatory properties by which they induce apoptosis of T and NK cells, via Fas/FasL pathway, and escape inflammatory response by up-regulating c-FLIP system.

Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells / CARNEVALE, Gianluca; Carpino, Guido; Cardinale, Vincenzo; PISCIOTTA, ALESSANDRA; RICCIO, Massimo; Bertoni, Laura; GIBELLINI, Lara; DE BIASI, SARA; Nevi, Lorenzo; Costantini, Daniele; Overi, Diletta; COSSARIZZA, Andrea; DE POL, Anto; Gaudio, Eugenio; Alvaro, Domenico. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017), pp. N/A-N/A. [10.1038/s41598-017-14838-3]

Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells

CARNEVALE, Gianluca;PISCIOTTA, ALESSANDRA;RICCIO, Massimo;Bertoni, Laura;GIBELLINI, Lara;DE BIASI, SARA;COSSARIZZA, Andrea;DE POL, Anto;
2017-01-01

Abstract

Intrahepatic cholangiocarcinoma (iCCA) represents a heterogeneous group of malignancies emerging from the biliary tree, often in the context of chronic bile ducts inflammation. The immunological features of iCCA cells and their capability to control the lymphocytes response have not yet been investigated. The aims of the present study were to evaluate the interaction between iCCA cells and human peripheral blood mononuclear cells (PBMCs) and the role of Fas/FasL in modulating T-cells and NK-cells response after direct co-culture. iCCA cells express high levels of Fas and FasL that increase after co-culture with PBMCs inducing apoptosis in CD4(+), CD8(+) T-cells and in CD56(+) NK-cells. In vitro, c-FLIP is expressed in iCCA cells and the co-culture with PBMCs induces an increase of c-FLIP in both iCCA cells and biliary tree stem cells. This c-FLIP increase does not trigger the caspase cascade, thus hindering apoptotis of iCCA cells which, instead, underwent proliferation. The increased expression of Fas, FasL and c-FLIP is confirmed in situ, in human CCA and in primary sclerosing cholangitis. In conclusion our data indicated that iCCA cells have immune-modulatory properties by which they induce apoptosis of T and NK cells, via Fas/FasL pathway, and escape inflammatory response by up-regulating c-FLIP system.
31-ott-2017
7
1
N/A
N/A
Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells / CARNEVALE, Gianluca; Carpino, Guido; Cardinale, Vincenzo; PISCIOTTA, ALESSANDRA; RICCIO, Massimo; Bertoni, Laura; GIBELLINI, Lara; DE BIASI, SARA; Nevi, Lorenzo; Costantini, Daniele; Overi, Diletta; COSSARIZZA, Andrea; DE POL, Anto; Gaudio, Eugenio; Alvaro, Domenico. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 7:1(2017), pp. N/A-N/A. [10.1038/s41598-017-14838-3]
CARNEVALE, Gianluca; Carpino, Guido; Cardinale, Vincenzo; PISCIOTTA, ALESSANDRA; RICCIO, Massimo; Bertoni, Laura; GIBELLINI, Lara; DE BIASI, SARA; Nevi, Lorenzo; Costantini, Daniele; Overi, Diletta; COSSARIZZA, Andrea; DE POL, Anto; Gaudio, Eugenio; Alvaro, Domenico
File in questo prodotto:
File Dimensione Formato  
s41598-017-14838-3.pdf

Open access

Descrizione: Articolo
Tipologia: Versione pubblicata dall'editore
Dimensione 10.51 MB
Formato Adobe PDF
10.51 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1147070
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 19
social impact