Clinicopathological and Prognostic Significance of Tim-3 and Rel-B Expressions in Grade 4 Diffuse Gliomas.

Abstract

Aim: To assess the clinicopathological and prognostic significance of Tim-3, an immune checkpoint molecule, and Rel-B, an NF-?B subunit, in grade 4 diffuse glioma samples and their relationship with each other.

Material and methods: The demographic, radiologic, treatment, and prognostic data of patients diagnosed with grade 4 diffuse glioma between 2016 and 2019 were reviewed and recorded. Tim-3 and Rel-B were applied to the paraffin-embedded tissues by immunohistochemistry method. Tim-3 expression was grouped as immunoreactivity density score (IDS) (Low, High) and expression percentage ( < 12%, > 12%), while Rel-B expression was divided into positive and negative groups.

Results: Ninety-nine grade 4 diffuse glioma samples were detected, 8 of which were IDH-1 positive. Tim-3 was expressed only in immune cells around and inside the tumoral tissue, and expression was detected only in tumoral cells with Rel-B. Tim-3 IDS was found at lower levels (median 31.8) in IDH-1 positive cases and higher (median 158) in IDH-1 negative ones (p=0.020). A significant correlation was found between the Tim-3 IDS high group and Rel-B positivity (p=0.007). In the IDH-1 negative cohort, the univariate analysis revealed higher Tim-3 expression percentage and higher IDS were associated with better overall survival (OS) (p=0.041 and p=0.042 respectively) and progression-free survival (PFS) (p=0.023 and p=0.029 respectively), while in the multivariate analysis higher Tim-3 expression percentage was found to be an independent predictor for better OS (p=0.008) and PFS (p=0.022). Rel-B positive cases exhibited longer OS and PFS but the result was not statistically significant (p > 0.05).

Conclusion: Tim-3 can be a good prognostic predictor and treatment candidate, especially in patients with IDH-1 negative grade 4 diffuse gliomas however, further studies with more cases are needed for Rel-B. The significant relationship between Tim-3 and Rel-B expressions supported the interaction between NF-?B and immune checkpoint pathways.