Clinicopathological implications of TIM3+ tumor-infiltrating lymphocytes and the miR-455-5p/Galectin-9 axis in skull base chordoma patients

• Published in: Cancer Immunology, Immunotherapy Vol. 68; no. 7; pp. 1157 - 1169
• Main Authors: Zhou, Jinpeng, Jiang, Yang, Zhang, Haiying, Chen, Lian, Luo, Peng, Li, Long, Zhao, Junshuang, Lv, Fei, Zou, Dan, Zhang, Ye, Jing, Zhitao
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2019; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Cancer Research; Child; Chordoma - genetics; Chordoma - immunology; Chordoma - mortality; Chordoma - pathology; Disease-Free Survival; Female; Follow-Up Studies; Galectin-9; Galectins - genetics; Galectins - immunology; Galectins - metabolism; Gene Expression Regulation, Neoplastic - immunology; Hepatitis A Virus Cellular Receptor 2 - metabolism; Humans; Immunohistochemistry; Immunology; Lymphocyte Count; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical prognosis; Medicine; Medicine & Public Health; MicroRNAs - metabolism; Middle Aged; Mucin; Multivariate analysis; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - immunology; Oncology; Original; Original Article; Prognosis; Retrospective Studies; Skull; Skull Base Neoplasms - immunology; Skull Base Neoplasms - mortality; Skull Base Neoplasms - pathology; Survival Analysis; Tumor-infiltrating lymphocytes; Young Adult; miR-455-5p; TIM3; FOXp3; Skull base chordoma; CD8; Galectin–9
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-019-02349-1

Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan–Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion ( p  = 0.019), Karnofsky performance status (KPS) score ( p  = 0.017), and total TIL count ( p  < 0.001); downregulation of miR-455-5p was correlated with tumor invasion ( p  = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3) + TIL count was associated with chordoma invasion ( p  = 0.010) and KPS score ( p  = 0.037). Furthermore, multivariate analysis indicated that only TIM3 + TIL density was an independent prognostic factor for LRFS ( p  = 0.010) and OS ( p  = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.