Cytotoxic T lymphocyte antigen-4 (CTLA-4) expression in chordoma and tumor-infiltrating lymphocytes (TILs) predicts prog
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RESEARCH ARTICLE
Cytotoxic T lymphocyte antigen‑4 (CTLA‑4) expression in chordoma and tumor‑infiltrating lymphocytes (TILs) predicts prognosis of spinal chordoma G. He1 · X. Liu1 · X. Pan1 · Y. Ma2 · X. Liu1 Received: 3 February 2020 / Accepted: 10 May 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract Purpose Chordoma is a rare tumor of the skeletal system that is characterized by a high recurrence rate and treatment resistance. Given the common finding of immune dysregulation in chordoma, immunotherapy has emerged as potential treatment option. As an important immune checkpoint regulator, we evaluated cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression and its prognostic significance for patients with chordoma of the spine. Methods CTLA-4 expression was analyzed immunohistochemically in 32 chordoma tissues and 14 nucleus pulposus tissues to examine the specificity of CTLA-4 expression in chordoma. Univariate log-rank analysis was used to evaluate the association of CTLA-4 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) with survival. Cox multivariate analysis was used to identify independent factors of survival. Results Positive CTLA-4 expression was observed in all of the TILs and tumor cell cytoplasm, and partial in the membrane or in both the membrane and nucleus, with a markedly higher positivity rate than that observed in normal nucleus tissues. Higher CTLA-4 expression in the tumor but not in TILs was significantly associated with shorter continuous disease-free survival (CDFS) and overall survival (OS). CTLA-4 expression in tumor cells and TILs were independent predictors for CDFS, whereas only tumor cell expression was a significant predictor of OS. Furthermore, the combination of CTLA-4 expression in the tumor and TILs had higher prognostic value. Conclusions Targeting CTLA-4 may be a potential novel therapeutic strategy for chordoma patients. Keywords CTLA-4 · Immunohistochemistry · Chordoma · TILs · Prognosis Abbreviations CDFS Continuous disease-free survival CTLA-4 Cytotoxic T lymphocyte antigen 4 DAB Diaminobenzidine FCEP Favorable CTLA-4 expression profile IHC Immunohistochemistry
LSS Lumbar spinal stenosis LDH Lumbar disk herniation OS Overall survival PD-1 Programmed cell death protein 1 TILs Tumor-infiltrating lymphocytes
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12094-020-02387-7) contains supplementary material, which is available to authorized users. * X. Liu [email protected] 1
Department of Orthopedics, North Garden Street, Peking University Third Hospital, No. 49, Haidian District, Beijing 100191, People’s Republic of China
The Center for Pain Medicine, North Garden Street, Peking University Third Hospital, No. 49, Haidian District, Beijing 100191, China
2
Chordoma is an extremely rare malignant mesenchymal tumor of the skull base and axial skeleton that is considered to originate from notochordal remnants. Chordoma is typically characterized
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