A routine blood test, cheaper than a coffee, might hold the key to understanding brain tumor aggression.
Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant cancers known to medicine. Despite decades of research, the median survival for patients often remains a grim 12 to 18 months, with fewer than 5% of patients alive five years after diagnosis.
12-18
Months Median Survival
<5%
5-Year Survival Rate
In the face of this daunting challenge, scientists are turning to a surprisingly simple and accessible tool: the neutrophil-to-lymphocyte ratio (NLR). This metric, derived from a routine blood test, measures the balance between two key white blood cells—neutrophils, which promote inflammation, and lymphocytes, which coordinate targeted immune attacks. Emerging evidence suggests that this simple ratio could provide a powerful glimpse into a patient's prognosis, guiding more personalized and effective treatment strategies 1 3 7 .
To understand why NLR is significant, one must first understand the immune system's complex relationship with cancer.
The first responders of the immune system. In large numbers, they can create a pro-inflammatory environment that paradoxically fuels tumor growth, suppresses the immune system, and aids cancer in spreading.
Particularly T-cells and natural killer (NK) cells, are essential for recognizing and destroying cancer cells.
A high NLR indicates a state where pro-tumor inflammation is dominating over the body's anti-tumor defense. This imbalance is linked to poorer survival across many cancers, and glioblastoma is no exception 2 6 . A high neutrophil-to-lymphocyte ratio suggests an immunosuppressed state, where the body is less capable of mounting an effective attack against the tumor.
Immune cells: Neutrophils and lymphocytes play crucial roles in cancer progression
While many studies have looked at a single pre-operative NLR value, recent research has revealed that the dynamic change in NLR throughout treatment may be even more telling.
A 2025 study published in Neuro-Oncology Advances meticulously investigated how NLR changes before and after surgery impact patient survival 2 . This study was crucial because it focused specifically on a uniform group of IDH wild-type glioblastoma patients and accounted for factors like dexamethasone use, a steroid that can influence blood counts.
The researchers retrospectively analyzed 230 glioblastoma patients, collecting their blood data at multiple time points 6 :
NLR was calculated from blood counts taken within one month before surgery, as well as on the two days immediately preceding the operation.
NLR was again calculated using blood counts from the first seven days after surgery.
The key metric, ΔNLR (delta-NLR), was defined as the average post-operative NLR minus the average pre-operative NLR. This measured the magnitude of the ratio's shift following the surgical intervention 6 .
The study's findings were striking. Patients were grouped based on whether their NLR increased by a large amount (ΔNLR ≥ 6) or a smaller amount (ΔNLR < 6). The results, summarized in the table below, show a dramatic difference in outcomes.
| ΔNLR Group | Median Overall Survival | Statistical Significance |
|---|---|---|
| Large Increase (ΔNLR ≥ 6) | 196 days | p = 0.01 |
| Smaller Increase (ΔNLR < 6) | 304 days |
This analysis revealed that a large rise in NLR after surgery was not only associated with decreased survival but also with a higher rate of post-surgical complications like infections and blood clots 6 . This suggests that the physiological stress of surgery may trigger a systemic inflammatory response in some patients, which inadvertently supports the tumor and worsens prognosis.
The findings from this single experiment are not an isolated case. They fit into a consistent pattern observed across the global scientific community, as shown in the following table of selected studies.
| Study / Source (Year) | Key Finding on High NLR | Context / Timing |
|---|---|---|
| Bratisl Lek Listy (2024) 1 | 1.05x higher risk of death per 1-unit NLR increase | Pre-treatment value |
| PMC (2022 Meta-Analysis) 3 | Significant association with lower survival (HR: 1.46) | Pre-treatment & pre-operative |
| Spandidos Publ. (2018) 5 | Trend toward worse survival (13.2 vs 10.7 mos), not statistically significant | Pre-treatment |
| PMC (2019 Meta-Analysis) 7 | Connected with unfavorable overall survival (HR: 1.43) | Various timings |
A 2022 meta-analysis, which pools data from multiple studies to reach a more robust conclusion, confirmed that a high pre-treatment NLR is significantly associated with lower overall survival in glioblastoma patients 3 . Another 2019 meta-analysis of 16 studies involving over 2,275 patients came to a similar conclusion, cementing NLR's role as a credible prognostic marker 7 .
To conduct the kind of research detailed above, scientists rely on a suite of tools and reagents. The following table outlines some of the essential components used in the featured experiment and similar studies in this field.
| Tool / Reagent | Primary Function in Research |
|---|---|
| Automated Hematology Analyzer | Precisely counts neutrophils and lymphocytes in blood samples to calculate the NLR. |
| Electronic Medical Record (EMR) Systems | Provides retrospective data on patient treatment, dexamethasone doses, and survival outcomes. |
| Statistical Software (e.g., SPSS, R) | Analyzes complex data to find correlations between NLR, patient characteristics, and survival. |
| MRI (Magnetic Resonance Imaging) | Evaluates the extent of surgical resection and monitors for tumor recurrence. |
| Dexamethasone | A corticosteroid used to manage brain swelling in patients; its dose is tracked as it can influence blood counts. |
Precise blood cell counting
Patient data management
Data analysis and visualization
The exploration of NLR is moving beyond a simple snapshot. Researchers are now validating the power of dynamic NLR (dNLR)—the ratio's change over the entire treatment course, including after chemoradiation 2 . Studies have shown that a post-treatment dNLR ≥ 1.3 is significantly associated with a worse prognosis, potentially making it a more reliable marker than a single measurement 2 .
While not yet a perfect standalone tool, the neutrophil-lymphocyte ratio represents a significant step forward. It is an inexpensive, accessible, and repeatable biomarker that offers a window into the unique biology of a patient's cancer.
As research continues, the hope is that integrating NLR with other biomarkers like MGMT promoter methylation and IDH mutation status will allow oncologists to construct highly accurate prognostic maps for each individual. This powerful combination of simple blood tests and advanced genomics promises to usher in a more personalized and effective era in the battle against glioblastoma, finally beginning to alter the once-inevitable course of this devastating disease.