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

• Published in: European journal of cancer (1990) 2013-06, Vol.49 (9), p.2233-2242
• Main Authors: 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, Spagnoli, Giulio C, Tornillo, Luigi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - metabolism; B7-H1 Antigen - metabolism; Biological and medical sciences; Biomarkers, Tumor - metabolism; CD8-Positive T-Lymphocytes - metabolism; Colonic Neoplasms - metabolism; Colonic Neoplasms - mortality; DNA Mismatch Repair - physiology; Female; Hematology, Oncology and Palliative Medicine; Human colorectal cancer; Humans; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Overall survival; PD-L1; Pharmacology. Drug treatments; Prognosis; Prognostic factors; Rectal Neoplasms - metabolism; Rectal Neoplasms - mortality; Tissue Array Analysis; Tissue microarrays; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.02.015

Abstract 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.