Programmed cell death ligand 1 (PD-L1, CD274) in cholangiocarcinoma – correlation with clinicopathological data and comparison of antibodies

Mark KriegsmannView ORCID ID profile,
Stephanie Roessler,
Katharina Kriegsmann,
Marcus Renner,
Rémi Longuespée,
Thomas Albrecht,
Moritz Loeffler,
Stephan Singer,
Arianeb Mehrabi,
Monika Nadja Vogel,
Anita Pathil,
Bruno Köhler,
Christoph Springfeld,
Christian Rupp,
Karl Heinz Weiss and
Benjamin GoeppertEmail author

BMC Cancer201919:72

https://doi.org/10.1186/s12885-018-5254-0

Received: 13 June 2018
Accepted: 26 December 2018
Published: 15 January 2019

Open Peer Review reports

Abstract

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 (κ = 0.44) and poor between 28-8 and SP142 (κ = 0.13), as well as SP142 and SP263 (κ = 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.