Fig. 6
Modulation of response to tepotinib and irradiation alone or in combination by loss of adaptive immunity. A. Rag1−/− mice were intracranially implanted with SMA-560 glioma cells, treated daily with 100 mg/kg tepotinib from day 6 on or solvent, or with a single dose of 10 Gy on day 7, or in combination. Kaplan–Meier survival curves are shown. B,C. GL-261 wildtype cells were intracranially implanted into C57/BL6 Rag1−/− mice (B), or GL-261 Met knockout cells were intracranially implanted into C57/BL6 wildtype mice (C). Mice were treated daily with 100 mg/kg tepotinib or solvent from day 6 on, or with a single dose of 10 Gy on day 7, or a combination thereof, and Kaplan–Meier survival curves are shown (++ p < 0.01, versus control). D. Illustration of median survival differences between treatment groups in the GL-261 model (n.d., not defined, > 50% of animals cured; *** p < 0.0001, versus control; ### p < 0.0001, versus tepotinib; +++ p < 0.0001, versus radiotherapy). Symptomatic animals implanted with GL-261 wildtype or Met knockout cells were euthanized, the brains removed, cut into thin slices and stained with H&E or for CD31 (T, tumor; B, brain). Representative images are shown (left), stainings were quantified using Image J (right) (** p < 0.01, relative to control; AU, arbitrary units)