IMMU-06. H-FERRITIN AFFECTS IMMUNE CELL INFILTRATION INTO THE GLIOBLASTOMA TUMOR MICROENVIRONMENT IN A SEX-BIASED MANNER

Abstract Glioblastoma (GBM) is an aggressive brain cancer that is sexually dimorphic in nature, with females less susceptible to developing it, responding better to therapy, and gaining a survival advantage. Iron metabolism is also sexually dimorphic and has been shown previously to contribute to sex bias in GBM. Ferritin is an iron-storing protein that has elevated expression in tumor cells and is essential to GBM growth. Here, we used an in vivo GBM model consisting of heterozygous FTH1 knockdown (FTH1-KD) mice and GL261 cells to study the role of host ferritin in GBM progression. We have previously published that FTH1 knockdown in female mice decreased overall survival compared to WT (P = 0.03). This work delves into potential mechanisms that contribute to this survival difference. GBM was induced in 6-8 weeks-old mice by injecting 2*10^4 GL261 cells intracranially by a stereotaxic apparatus. The tumor volume was measured 3 weeks post-injection by magnetic resonance imaging, followed by image segmentation. We observed that FTH1 knockdown did not affect tumor volume. Flow cytometry was used to examine the immune infiltrating cells (CD45high) population in the tumor-bearing hemisphere. In females, there was an increase in CD11b+ cells in FTH1KD mice compared to WT mice (P = 0.0607). Similarly, Female FTH1-KD mice had a lower T cell (CD3+) population than Female WT mice (P = 0.0033). This decrease in infiltrating CD3 cells was due to a reduction of CD4 T cells (CD3+ CD4+) in female FTH1-KD mice compared to female WT mice (P = 0.0375). We observed no difference in CD8 T cells (CD3+ CD8+). These data indicate that host ferritin affects immune infiltration into GBM cells in a sex-biased manner.