Expression of programmed cell death ligand 1 (PD-L1) and prevalence of tumor-infiltrating lymphocytes (TILs) in chordoma

Yong Feng,Ivan Chebib,Gregory Cote,Henry Mankin,Yan Gao,Francis Hornicek,Jacson Shen,Zhenfeng Duan,Edwin Choy,Yunfei Liao

doi:10.18632/oncotarget.3576

Abstract

Chordomas are primary malignant tumors of the notochord that are resistant to conventional chemotherapy. Expression of programmed cell death ligand 1 (PD-L1), prevalence of tumor-infiltrating lymphocytes (TILs), and their clinical relevance in chordoma remain unknown. We evaluated PD-L1 expression in three chordoma cell lines and nine chordoma tissue samples by western blot. Immunohistochemical staining was performed on a chordoma tissue microarray (TMA) that contained 78 tissue specimens. We also correlated the expression of PD-L1 and TILs with clinical outcomes. PD-L1 protein expression was demonstrated to be induced by IFN-γ in both UCH1 and UCH2 cell lines. Across nine human chordoma tissue samples, PD-L1 protein was differentially expressed. 94.9% of chordoma samples showed positive PD-L1 expression in the TMA. The expression score of PD-L1 for metastatic chordoma tumors was significant higher as compared with non-metastatic chordoma tumors. Expression of PD-L1 protein significantly correlates with the presence of elevated TILs, which correlates with metastasis. In summary, our study showed high levels of PD-L1 are expressed in chordoma, which is correlated with the prevalence of TILs. The current study suggests targeting PD-L1 may be a novel immunotherapeutic strategy for chordoma clinical trials.

Highlights

Chordoma, an extremely rare cancer presumably originating from notochord, accounts for 20% of primary spine tumors and 1- 4% of primary malignant bone tumors [1, 2]
We demonstrate that all chordoma cell lines UCH1, UCH2, and CH22 express PD-L1 protein
Consistent with previous studies that showed the ability of IFN-γ to up regulate expression of PD-L1 [28], treatment of UCH1 and UCH2 cell lines with IFN-γ induced significantly higher levels of PD-L1 protein expression

Summary

Introduction

An extremely rare cancer presumably originating from notochord, accounts for 20% of primary spine tumors and 1- 4% of primary malignant bone tumors [1, 2]. Epidemiological studies suggest that chordoma affects roughly one in a million individuals; approximately 300 new cases of chordoma are diagnosed in the US per year with an overall median survival of about six years [3]. The standard treatment for these tumors is en-bloc resection accompanied by radiotherapy given both before and after surgery; the critical anatomic location (spread along critical bony and neural structures) and the commonly large tumor size make clinical management of these patients difficult. Distant metastasis occurs in 20-40% of patients with chordoma of the spine and in less than 10% of patients with skull-base tumors, with the median survival time after metastasis around one year [35]. Development of novel therapeutic strategies is critical for this patient population

Objectives

Methods

Results

Conclusion