Clinicopathologic implications of CD8+/Foxp3+ ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients

Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor...

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Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2018-02, Vol.67 (2), p.209-224
Main Authors: Zou, Ming-Xiang, Guo, Ke-Miao, Lv, Guo-Hua, Huang, Wei, Li, Jing, Wang, Xiao-Bin, Jiang, Yi, She, Xiao-Ling
Format: Article
Language:English
Subjects:
Adult
Aged
B7-H1 Antigen - biosynthesis
B7-H1 Antigen - genetics
B7-H1 Antigen - immunology
Cancer Research
Case-Control Studies
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Chordoma - genetics
Chordoma - immunology
Chordoma - pathology
Female
Forkhead Transcription Factors - immunology
Foxp3 protein
Humans
Immune checkpoint
Immunohistochemistry
Immunology
Lymphocytes
Lymphocytes, Tumor-Infiltrating - immunology
Male
Medical prognosis
Medicine
Medicine & Public Health
Metastases
MicroRNAs - biosynthesis
MicroRNAs - genetics
MicroRNAs - immunology
Middle Aged
miRNA
Multivariate analysis
Oncology
Original
Original Article
Patients
PD-1 protein
PD-L1 protein
Phenotypes
Polymerase chain reaction
Prognosis
Signal transduction
Spinal Neoplasms - genetics
Spinal Neoplasms - immunology
Spinal Neoplasms - pathology
Tumor cells
Tumor Microenvironment - immunology
Tumor-infiltrating lymphocytes
Young Adult
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Summary:Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3 + , CD8 + , PD-1 + and PD-L1 + ) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. MiRNAs microarray and bioinformatical analysis were used to identify miRNAs potentially regulating PD-L1 expression, which were further validated by quantitative RT-PCR. miR-574-3p was identified to potentially regulate PD-L1 expression in chordoma, which inversely correlated with PD-L1. Positive PD-L1 expression on tumor cells was associated with advanced stages ( P  = 0.041) and TILs infiltration ( P  = 0.005), whereas decreased miR-574-3p level correlated with higher muscle invasion ( P  = 0.012), more severe tumor necrosis ( P  = 0.022) and poor patient survival. Importantly, a patient subgroup with PD-L1 + /miR-574-3p low chordoma phenotype was significantly associated with worse local recurrence-free survival (LRFS) ( P  = 0.026). PD-1 + TILs density was associated with surrounding muscle invasion ( P  = 0.014), and independently portended poor LRFS ( P  = 0.040), while PD-L1 + TILs showed tendencies of less aggressive clinical outcomes. Multivariate analysis of OS only found CD8 + /Foxp3 + ratio to be independent prognostic factor ( P  = 0.022). These findings may be useful to stratify patients into prognostic groups and provide a rationale for the use of checkpoint blockade therapy, possibly by administering miR-574-3p mimics, in spinal chordoma.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-017-2080-1