Clinical impact of programmed cell death ligand 1 expression in colorectal cancer

Droeser, Raoul A.; Hirt, Christian; Viehl, Carsten T.; Frey, Daniel M.; Nebiker, Christian; Huber, Xaver; Zlobec, Inti; Eppenberger-Castori, Serenella; Tzankov, Alexander; Rosso, Raffaele; Zuber, Markus; Muraro, Manuele Giuseppe; Amicarella, Francesca; Cremonesi, Eleonora; Heberer, Michael; Iezzi, Giandomenica; Lugli, Alessandro; Terracciano, Luigi; Sconocchia, Giuseppe; Oertli, Daniel; ... (2013). Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. European journal of cancer, 49(9), pp. 2233-2242. Elsevier 10.1016/j.ejca.2013.02.015

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BACKGROUND Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed. MATERIALS AND METHODS A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression. RESULTS Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P=0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P=0.0001) and validation (P=0.03) sets. A similar trend (P=0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n=42) were found to be significantly associated (r=0.33, P=0.03). CONCLUSION PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Zlobec, Inti; Tzankov, Alexander; Lugli, Alessandro and Terracciano, Luigi

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0959-8049

Publisher:

Elsevier

Language:

English

Submitter:

Andrea Arnold

Date Deposited:

02 Apr 2014 16:59

Last Modified:

02 Apr 2014 16:59

Publisher DOI:

10.1016/j.ejca.2013.02.015

PubMed ID:

23478000

URI:

https://boris.unibe.ch/id/eprint/45961

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