TY  - JOUR
TI  - Programmed cell death ligand 1 (PD-L1, CD274) in cholangiocarcinoma ? correlation with clinicopathological data and comparison of antibodies
CY  - London ; Berlin, Heidelberg
KW  - PD-L1
KW  -  Cholangiocarcinoma
KW  -  CD274
KW  -  28?8
KW  -  SP142
KW  -  SP263
PB  - BioMed Central ; Springer
VL  - 19
IS  - 72
ID  - heidok25918
SN  - 1471-2407
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/25918/
SP  - 1
Y1  - 2019///
N2  - Background: Cholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there is still no established targeted therapeutic approach available. Non-surgical therapeutic agents are urgently needed, as most patients are non-eligible to surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading the immune system and has emerged as a new treatment option in several cancer entities. Recently, PD-L1 expression has been analyzed in comparably small CCA patient cohorts. However, a systematic validation of different PD-L1 antibodies has not been performed in CCA so far.

Methods: We stained a tissue microarray consisting of 170 patients, including 72 intrahepatic cholangiocarcinomas (iCCAs), 57 perihilar cholangiocarcinomas (pCCAs) and 41 distal cholangiocarcinomas (dCCAs) by immunohistochemistry and evaluated PD-L1 positivity in tumor and stromal cells. We analyzed three different PD-L1 antibodies (clones 28?8, SP142, and SP263) that are frequently used and recommended for predictive diagnostic testing in other cancer types.

Results: For PD-L1 antibody clone SP263, 5% of iCCAs, 4% of pCCAs and 3% of dCCAs exhibited PD-L1 expression on tumor cells, thereby showing the highest frequencies of PD-L1 positivity. Accordingly, highest PD-L1 positivity rates of stromal cells with 31% in iCCA, 40% in pCCA and 61% in dCCA were detected for clone SP263. Agreement of PD-L1 positivity in tumor cells was moderate for clone 28?8 and SP263 (? =?0.44) and poor between 28-8 and SP142 (? =?0.13), as well as  SP142 and SP263 (? =?0.11), respectively. Statistical analyses of PD-L1 expression (clone SP263) on tumor cells with clinicopathological data revealed a positive correlation with shortened overall survival in CCA patients.

Conclusions: Selection of appropriate PD-L1 antibodies and careful evaluation of immunohistochemical staining patterns have a significant impact on PD-L1 testing in CCA. Clinical trials are necessary to investigate the putative beneficial effects of PD-L1 targeted immunotherapy in CCA patients.
AV  - public
EP  - 10
JF  - BMC Cancer
A1  - Kriegsmann, Mark
A1  - Roessler, Stephanie
A1  - Kriegsmann, Katharina
A1  - Renner, Marcus
A1  - Longuespée, Rémi
A1  - Albrecht, Thomas
A1  - Loeffler, Moritz
A1  - Singer, Stephan
A1  - Mehrabi, Arianeb
A1  - Vogel, Monika Nadja
A1  - Pathil, Anita
A1  - Köhler, Bruno
A1  - Springfeld, Christoph
A1  - Rupp, Christian
A1  - Weiss, Karl Heinz
A1  - Goeppert, Benjamin
ER  -