Prognostic significance of neutrophil-to-lymphocyte ratio in glioblastoma

Abstract

A B S T R A C T Aim:The neutrophil-to-lymphocyte ratio (NLR) has prognostic value in patients with a variety of cancers. The purpose of this study was to investigate the prognostic value of NLR in patients with glioblastoma. Methods: A prospective study was conducted on patients receiving surgery for glioblastoma. Preoperative NLR was recorded and correlated with other prognostic factors and survival. Results: Fifty-one patients were included in the study. The mean NLR ratio was 6.7 ± 4.6. Using receiver operating characteristic curve analysis, an NLR cut-off value of 4.7 was determined to best predict survival. Patients with NLR ratios exceeding 4.7 differed significantly from those with NLR ratios ≤ 4.7 and were associated with reduced survival. Patients with gross total tumor excision had a median survival of 18 months, whereas the median survival time was 11 months in patients with subtotal tumor excision. No significant difference in survival was observed with respect to patient age, gender, Karnofsky performance status, or tumor location. Using multivariate analysis, NLR and extent of tumor resection were identified as factors with independent prognostic power. Conclusion: Neutrophil-to-lymphocyte ratio is an inexpensive, widely available biomarker of glioblastoma aggressiveness and should be used alongside current glioblastoma prognostic factors.

Serum immuno-biomarkers in gliomas

“…Current therapies to abrogate tumor immunosuppression and unleash T-cell mediated killing of GBM include: inhibitors of immune-checkpoints that are exploited by GBM to enhance tumor survival (therapeutic antibodies against CTLA-4 and PD-1, which are overexpressed in tumor-infiltrating lymphocytes, and against PD-L1, which is overexpressed on GBM cells and tumorinfiltrating immune cells); vaccination strategies against single or multiple tumor-associated peptides; infusion of autologous adoptive CAR T-cells primed against GBM-specific antigens; and inhibition of the immunomodulatory indoleamine 2,3-dioxygenase (IDO) pathway, which is also overexpressed in GBM. [3,5] Recent work by Alexiou et al [6,7] published in this journal contributes to the use of immune mediators as prognostic surrogates of GBM aggressiveness and survival and may be clinical indicators of which patients are likely to benefit in current and future immunotherapeutic trials.…”

“…In the first article, a prospective, single-institution, observational study of GBM patients treated with tumor resection followed by chemotherapy and radiation (under the Stupp regimen [8] ) for up to 1 year, Alexiou et al [6] demonstrate a lower neutrophilto-lymphocyte ratio (NLR) to be an independent prognostic predictor of survival. Using a cutoff value of NLR < 4.7, both overall survival (OS) and progressionfree survival (PFS) were significantly longer.…”

“…In another study by Berghoff et al [16] a single-center retrospective analysis ("Vienna cohort"), improved survival was not associated with TIL density (or PD-L1 overexpression), in contrast the other studies. Routine analysis of TILs is difficult in clinical settings, so it is crucial that the study of Alexiou et al [6,7] mirrors the use of serum kynurenine and tryptophan levels as another biomarker of the immunosuppressive effect of IDO catabolism in gliomas, which demonstrated prognostic significance for OS in a prospective, multi-center observational trial of GBM patients. [17] Taken together, the work of Alexiou et al, [6] Bambury et al, [9] and Han et al [15] elaborate upon the role of TILs in GBM via an easily obtainable, non-invasive, serum biomarker proxy.…”

“…Routine analysis of TILs is difficult in clinical settings, so it is crucial that the study of Alexiou et al [6,7] mirrors the use of serum kynurenine and tryptophan levels as another biomarker of the immunosuppressive effect of IDO catabolism in gliomas, which demonstrated prognostic significance for OS in a prospective, multi-center observational trial of GBM patients. [17] Taken together, the work of Alexiou et al, [6] Bambury et al, [9] and Han et al [15] elaborate upon the role of TILs in GBM via an easily obtainable, non-invasive, serum biomarker proxy. These papers reinforce and expand upon the paradigm that GBM is a lymphocyte-suppressing tumor as well as that lymphocyte down-regulation is itself a marker of an aggressive tumor pathology.…”

Immunotherapeutic strategies for glioma treatment

“…[5] GBM cases of increased survival after bacterial infection have been documented, whereas patients with neutrophil to lymphocyte ratio in the blood that exceeded 4.7 differ significantly from those with neutrophil to lymphocyte ratio lower than 4.7 and were associated with worse survival. [6,7] Nevertheless, GBM can evade by several mechanisms immune surveillance, such as loss of major histocompatibility complex (MHC) antigen expression that prevent their recognition by the CD8 + T cells. [8] CD8 + T cell cytotoxic activity has been considered key for tumor eradication and these cells have been detected in GBM tissue.…”