Back to Search
Start Over
Clinicopathologic implications of CD8 + /Foxp3 + ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2018 Feb; Vol. 67 (2), pp. 209-224. Date of Electronic Publication: 2017 Oct 20. - Publication Year :
- 2018
-
Abstract
- 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 <superscript>+</superscript> , CD8 <superscript>+</superscript> , PD-1 <superscript>+</superscript> and PD-L1 <superscript>+</superscript> ) 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 <superscript>+</superscript> /miR-574-3p <superscript>low</superscript> chordoma phenotype was significantly associated with worse local recurrence-free survival (LRFS) (P = 0.026). PD-1 <superscript>+</superscript> TILs density was associated with surrounding muscle invasion (P = 0.014), and independently portended poor LRFS (P = 0.040), while PD-L1 <superscript>+</superscript> TILs showed tendencies of less aggressive clinical outcomes. Multivariate analysis of OS only found CD8 <superscript>+</superscript> /Foxp3 <superscript>+</superscript> 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.
- Subjects :
- Adult
Aged
B7-H1 Antigen biosynthesis
B7-H1 Antigen genetics
Case-Control Studies
Chordoma genetics
Chordoma pathology
Female
Humans
Lymphocytes, Tumor-Infiltrating immunology
Male
MicroRNAs biosynthesis
MicroRNAs genetics
Middle Aged
Prognosis
Spinal Neoplasms genetics
Spinal Neoplasms pathology
Tumor Microenvironment immunology
Young Adult
B7-H1 Antigen immunology
CD8-Positive T-Lymphocytes immunology
Chordoma immunology
Forkhead Transcription Factors immunology
MicroRNAs immunology
Spinal Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 67
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 29051990
- Full Text :
- https://doi.org/10.1007/s00262-017-2080-1