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

• DOI: 10.1016/j.ejca.2013.02.015
• Publication Date: 2013-03-13T02:17:33Z
• Authors: Raoul A. Droeser; Christian Hirt; Carsten T. Viehl; Daniel M. Frey; Christian Nebiker; Xaver Huber; Inti Zlobec; Serenella Eppenbe...; Alexander Tzankov; Raffaele Rosso; Markus Zuber; Manuele Giuseppe ...; Francesca Amicarella; Eleonora Cremonesi; Michael Heberer; Giandomenica Iezzi; Alessandro Lugli; Luigi Terracciano; Giuseppe Sconocchia; Daniel Oertli; Giulio C. Spagnoli; Luigi Tornillo
• Keywords: Adult; Aged, 80 and over; Male; Rectal Neoplasms; Kaplan-Meier Estimate; CD8-Positive T-Lymphocytes; Middle Aged; Prognosis; DNA Mismatch Repair; B7-H1 Antigen; 3. Good health; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; 0302 clinical medicine; Antigens, Neoplasm; Tissue Array Analysis; Colonic Neoplasms; Biomarkers, Tumor; Humans; Female; Aged

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.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.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).PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.