Fig. 6. SMYD2 inhibition provokes a robust antitumor immune program and further enhanced by combination with radiotherapy.

(A) Scheme for the BALB/c mice bearing CT26 cells treated with SMYD2 inhibitor AZ505 or vehicle. IP injection every other day at a dose of 20 mg/kg from day 4. Body weight, tumor weight and tumor volume of CT26 tumors treated with or without AZ505. (B) Flow cytometry analysis of immune cells in CT26 tumors collected at day 13 with or without AZ505 from day 5, shown by percent of parent gates. (C) Representative images of H&E and IHC staining of γ-H2AX and CD8 in CT26 tumor tissues collected at day 13 with or without AZ505 from day 5. Scale bars, 30 μm. (D) Scheme for the BALB/c mice bearing CT26 cells treated with AZ505 and irradiation or AZ505 alone or irradiation alone or vehicle. IP injection of AZ505 every other day at a dose of 10 mg/kg from day 10 and local irradiation at a dose of 6 Gy once at day 10. (E) Body weight, tumor weight, and tumor volume of CT26 tumors from four groups above. (F) Representative images of H&E and IHC staining of γ-H2AX and CD8 in tissues from four groups above. IP injection every other day at a dose of 10 mg/kg and local irradiation at a dose of 6 Gy once at day 7. The tumor tissues were collected at day 13. Lower graphs of statistics for the percentage of positive cells within the tumors. Scale bars, 30 μm. (G) The expression of SMYD2 in tumors and adjacent normal tissues for indicated cancers from TCGA database of TIMER website. (H) Correlation of SMYD2 expression and the activated CD8 abundance for indicated cancers. The immune-related activated CD8 signatures were from the study of Charoentong et al. (55) and TISIDB website.