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

Cancer Immunol Immunother. 2019 Jul;68(7):1157-1169. doi: 10.1007/s00262-019-02349-1. Epub 2019 Jun 13.

Abstract

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.

Keywords: CD8; FOXp3; Galectin–9; Skull base chordoma; TIM3; miR-455-5p.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Chordoma / genetics
  • Chordoma / immunology
  • Chordoma / mortality
  • Chordoma / pathology*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Galectins / genetics*
  • Galectins / immunology
  • Galectins / metabolism
  • Gene Expression Regulation, Neoplastic / immunology
  • Hepatitis A Virus Cellular Receptor 2 / metabolism
  • Humans
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / immunology
  • Prognosis
  • Retrospective Studies
  • Skull Base Neoplasms / immunology
  • Skull Base Neoplasms / mortality
  • Skull Base Neoplasms / pathology*
  • Survival Analysis
  • Young Adult

Substances

  • Galectins
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • LGALS9 protein, human
  • MIRN455 microRNA, human
  • MicroRNAs