TY  - GEN
A1  - Hunger, Jessica
N2  - Gliomas are characterized by increased T cell exhaustion and poor T cell infiltration into the tumor as well as an overall highly immunosuppressive tumor microenvironment (TME). Response rates in preclinical glioma models and patients to promising new therapeutic approaches in the field of immunotherapies remain heterogenous. These include checkpoint blockade, peptide and mRNA vaccines and adoptive therapy with chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cells. This demonstrates the need for non-invasive tracking of T cell recruitment to the TME in order to monitor immunotherapies, adapt therapeutic strategies and predict treatment outcome. Iron oxide nanoparticles (NP) can be visualized non-invasively by magnetic resonance imaging (MRI) and dedicated MRI sequences such as T2* mapping. Using isolated murine T cell cultures I show that labeling of T cells with iron oxide NPs as contrast agents is feasible and does not impair T cell viability and functionality as assessed by cytokine secretion and antigen-specific killing activity in vitro. I demonstrate that adoptively transferred T cells can be visualized intratumorally in a murine glioma model by high field MRI at 9.4 Tesla with high sensitivity and that T cells can be tracked non-invasively in a time course of at least two weeks. Correlative methods include immunohistochemistry, flow cytometry, tissue clearing and light sheet microscopy. Tumor relaxation times at an early time point after adoptive cell transfer (ACT) were a predictor for tumor response or resistance, which demonstrates that non-invasive quantification of spatial and temporal T cell dynamics in the TME can facilitate immune cell monitoring to assess immunotherapy efficacy.
TI  - Non-invasive tracking of T cell recruitment to the tumor microenvironment in a murine glioma model by high field cellular magnetic resonance imaging
AV  - public
ID  - heidok33485
Y1  - 2023///
CY  - Heidelberg
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/33485/
ER  -