Fig. 7: ATM inhibition delays tumor growth and sensitizes tumors to PD-1 blockade and radiotherapy.

A, B 1 × 10⁶ 4T1 cells were orthotopically implanted into the right fourth mammary fat pads of 6–8-week-old female BALB/c mice. When the tumor volume reached about 100 mm³, mice received a 10 mg/kg dose of KU55933 or placebo via intraperitoneal injection every three days. Mice received intraperitoneal injections of 100 μg of anti-PD-1 (clone 29 F.1A12™; Bio X Cell) per injection or its isotype control (clone 2A3; Bio X Cell) on days 10, 17and 24. Radiation therapy was administered when the tumor volume of the mice reached approximately 300 mm³ (n = 5–7/group). A Treatment regimen and (B) mean tumor volume curves are shown. C, D 1 × 10⁶ EMT6 cells were orthotopically implanted into the right fourth mammary fat pads of 6–8-week-old female BALB/c mice and subjected to the identical treatment regimen. C Treatment regimen and (D) mean tumor volume curves are shown. *P < 0.05; **P < 0.01; ns, not significant, P > 0.05, by unpaired t test (B, D). E–L Representative images of immunohistochemical staining of all molecules expressed in 4T1 murine mammary tumor tissues (200 ×). (E) p-Atm low (H-score: 40); (F) p-Atm high (H-score: 110); (G) Tnf-α low (H-score: 30); (H) Tnf-α high (H-score: 120); (I) p-Stat1 low (H-score: 20); (J) p-Stat1 high (H-score: 220); (K) H-2 low (H-score: 40); (L) H-2 high (H-score: 120). M–T Representative images of immunohistochemical staining of all molecules expressed in EMT6 murine mammary tumor tissues (200 ×). M p-Atm low (H-score: 30); (N) p-Atm high (H-score: 120); (O) Tnf-α low (H-score: 25); (P) Tnf-α high (H-score: 180); (Q) p-Stat1 low (H-score: 20); (R) p-Stat1 high (H-score: 140); (S) H-2 low (H-score: 65); (T) H-2 high (H-score: 220).