Figure 1

Cabozantinib inhibits the growth, alters the phenotype and increases the sensitivity of MC38-CEA cells to T cell-mediated killing. (A) MC38-CEA cells were treated with 2.5 μg/mL cabozantinib or vehicle for 1, 3, and 5 days then assayed for growth and viability. Inset panel: MET and VEGFR2 expression of MC38-CEA cells. (B) MC38-CEA cells were exposed to 2.5 μg/mL cabozantinib or vehicle for 24 h, then analyzed by flow cytometry for surface expression of CEA, MHC-I (H-2K^b, H-2D^b), ICAM-1, Fas, and calreticulin. Percent positivity and mean fluorescence intensity, in parentheses, are shown. Values in bold denote an increase of >40% relative to vehicle-treated cells. (C, D) MC38-CEA cells treated with cabozantinib (black bars) or vehicle (open bars) or left untreated (gray bars) for 24 h were labeled with ¹¹¹In, then coincubated with CTLs specific for CEA (C) or gp70 (D) for 18 h at a ratio of 30:1. Bars indicate mean ± SEM. from quadruplicate measurements. Statistical analyses were done by Student's t test. * = P <0.01. Data are representative of 3 independent experiments.