Background
Glioblastoma (GBM) remains uniformly fatal with a median overall survival (OS) of <21 months. There is a disconnect between multiple promising preclinical findings and disappointing clinical trial results. A contributing factor could be that preclinical studies rely on young 6–8 week old mice while the median patient age at diagnosis of GBM is 64 years. Previous preclinical studies have shown that aged GBM bearing mice have reduced OS in comparison to younger mice, and that the response to immunotherapy in aged tumor bearing mice is inferior. To further understand this issue we have conducted immune profiling in the brain and periphery of young and aged mice
Methods
Young (6–8 week) or aged (11 month+) C57BL/6 mice were implanted intracranially with CT2A tumors. The immune profiles of the local immune environment (brain) and peripheral immune cells (spleen and blood) of either naïve or tumor-bearing mice was determined by flow cytometry on day 14 post tumor implantation.
Results
In this study, we observed higher overall brain weights of older mice compared to condition matched young mice. Within the naïve groups, the proportions of immune cells were significantly lower in the brains older mice: CD8+ T cells, p<0.008; B cells, p<0.04; and microglia, p<0.02. The presence of a brain tumor counteracted the effects of age on brain immune composition of CD8+ T cells, B cells and microglia but greatly reduced the eosinophil population (p<0.008) in aged mice. This modulation of eosinophils is also reflected peripherally, with fewer eosinophils in the spleen of aged tumor bearing mice (p<0.008).
Conclusions
We observed differences in immune profiles of the brain and periphery of the tumor-bearing aged mice in comparison to tumor-bearing young mice. Of particular note are a reduction in eosinophils in aged mice, which is known to result in worse overall survival in GBM. These differences may impact the effectiveness of immunotherapy in aged populations. Subsequent studies will include the functional activity of immune cells from both young and aged tumor bearing mice and interrogating changes in specimens from our immunotherapy clinical trials conducted in older and younger patients with GBM