NIMG-51. 18KDA TRANSLOCATOR PROTEIN (TSPO) DECLINES IN TUMOR AND IMMUNE CELLS DURING PROGRESSION OF EXPERIMENTAL GLIOBLASTOMA

Laura Bartos,Matthias Brendel,Lukas Gold,Nathalie Albert,Denise Messerer,Jens Blobner,Stefanie Quach,Melissa Antons,Peter Bartenstein,Joerg-Christian Tonn,Philipp Beumers,Markus Riemenschneider,Karin Wind,Sebastian Kunte,Sabrina Kirchleitner,Louisa Von Baumgarten,Lea Kunze,Adrien Holzgreve,Lorraine Weidner

doi:10.1093/neuonc/noac209.669

Abstract

Abstract Glioblastoma combines a lack of immunogenicity with a highly immunosuppressive tumor microenvironment (TME), including both tumor and immune cells. However, biomarkers that allow monitoring of the immune phenotype are still lacking. Hence, we investigated the 18kDa translocator protein (TSPO) during tumor progression in an experiential glioblastoma mouse model (SB28) mimicking human TME. We used TSPO-PET imaging ([18F]GE-180) and in vivo measures of single cell tracer uptake between days 6 and 18 after inoculation to study alterations and dependence of TSPO in tumor and peripheral organs in SB28 mice (n= 27) in comparison to sham controls (n= 11). CSF1R inhibition was applied to deplete tumor associated microglia/macrophages (TAM) followed by withdrawal to induce immune cell rebound (PLX5622 day -20 to day 6, n= 3). Compared to sham, TSPO-PET signals were distinctly elevated in tumor (+83%, p&lt; 0.001), heart (+35%, p&lt; 0.05), lung (+42%, p&lt; 0.01) and bone (+26%, p&lt; 0.05) of SB28 mice at day 6. TSPO-PET increases were lower at day 18 (tumor: +52%, p&lt; 0.05; all organs &lt; +15%, n.s.). The tumor TSPO-PET signal was strongly coupled with TSPO-PET signal in peripheral organs (all R≥ 0.88, all p&lt; 0.001). Single tumor cells and TAM showed strong early increases of TSPO tracer uptake at day 6 (tumor: 32-fold, TAM: 8.5-fold) and a decline of these increases at day 18 (tumor: 2.4-fold, TAM: 1.7-fold) when compared to sham microglia. Immune cell rebound restored TSPO tracer uptake in TAM (+120%, p&lt; 0.01) but not in tumor cells (-24%, n.s.) when compared to therapy-naïve SB28 mice. TSPO declines in tumor cells and TAM during progression of experimental glioblastoma. TSPO in peripheral organs could serve as a supportive indicator of declining immune response in glioblastoma. CSF1R inhibition and reinitiation yields specific restoring of TSPO in TAM and could serve as immunomodulatory therapy strategy.

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