期刊
EUROPEAN JOURNAL OF CANCER
卷 49, 期 9, 页码 2233-2242出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2013.02.015
关键词
Human colorectal cancer; PD-L1; Prognostic factors; Overall survival; Tissue microarrays
类别
资金
- Swiss National Fund for scientific research (SNF) [PP00P3-133699, 31003A-122235]
- Italian Association for Cancer Research (AIRC) IG Grant [10555]
- Swiss National Science Foundation (SNF) [31003A-122235, PP00P3_133699] Funding Source: Swiss National Science Foundation (SNF)
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)-gamma 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. (C) 2013 Elsevier Ltd. All rights reserved.
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