FIGURE 6 from Inhibition of Aurora Kinase Induces Endogenous Retroelements to Induce a Type I/III IFN Response via RIG-I

Alisertib induces IFN in tumors and depends on immune compartment and tumor-expressed Sting for efficacy in vivo. A, Alisertib and decitabine inhibit growth in HCT116 xenografts. Growth curves of HCT116 tumors in mice treated with vehicle, 30 mg/kg alisertib, or 0.5 mg/kg decitabine. B, IFN is induced in tumors after AURKi or DNMTi administration to mice. qPCR of IFNβ or IFNλ1 from endpoint tumors from mice in A. C, Alisertib inhibits tumor growth of CT26 cells. Growth curves of CT26 tumors in mice treated with vehicle or 20 mg/kg alisertib, 5 mice per group. D, Alisertib administration induced IFN and IFN signature genes in CT26 tumors. qPCR of Ifnβ, Ifit1 or Ifit3 from endpoint tumors from mice in C. E, Alisertib inhibits growth of CT26 tumors in WT but not immune-deficient mice. Growth curves of CT26 tumors grown in NSG or WT Balb/c mice, 10 mice per group, treated with PBS vehicle or alisertib. F,Ifnβ is induced by alisertib treatment of WT or immune-deficient mice. qPCR of Ifnβ from midpoint tumors (day 7) or endpoint tumors (day 15) from mice in E. G, Alisertib treatment causes an influx of CD8⁺ cells into CT26 tumors. Quantification and representative images of CD8 IHC from endpoint tumors from WT mice treated with vehicle or alisertib. H, Alisertib depends on Sting expression in CT26 cells to inhibit tumor growth. Growth curves of CT26 NTC control pooled clones or Sting KO pooled clones implanted into WT Balb/c mice, treated with 20 mg/kg alisertib or vehicle control (13 mice per group). I, Sting KO antagonizes the effects of alisertib on IFN signature genes. qPCR of Ifnβ, Ifit3, or Cxcl10 from endpoint tumors from mice in H or from the same CT26 WT or Sting KO cell lines grown in vitro for 5 days with or without µmol/L alisertib.