Fig. 1: Enhancement of chemoradiation efficacy by the TGFβRI inhibitor, LY2157299, depends on CD8α⁺ cells in CT26 tumors.

a Treatment schema in the CT26 tumor model. Six to eight-week-old BALB/c mice were implanted subcutaneously in the left flank with 2 × 10⁵ CT26 tumor cells. Seven days following implant animals were randomized based on tumor size; vehicle control or LY2157299 (LY) compound were administered by oral gavage twice daily every 12 h at 150 mg/kg for 7 consecutive days. At day 14, some mice received 15 radiation treatments of 2 Gy, delivered Monday through Friday, targeted to tumor tissue along with 25 mg/kg injections of 5-fluorouracil (5FU) chemotherapy administered intraperitoneally on days 14, 16, and 18. LY treatment groups resumed BID oral dosing from days 21–27. b Mean tumor growth (i) and survival (ii) measured 3 times per week up to 100 days or death. For (i), p-values are a comparison between RT + 5FU (blue dots) and RT + 5FU + LY (red squares) using an unpaired, two-tailed t-test, and values are as follows for days 7–21: 0.059 (NS), 0.0086 (**), 0.0001(***), 0.0048 (**), 0.039(*), 0.042(*), 0.0068(**). For (ii), p-values for survival were derived using log-rank test. Vehicle (open circle) vs. RT + 5FU = 0.023(*), vehicle vs. RT + 5FU + LY < 0.0001(****), RT + 5FU vs. RT + 5FU + LY = 0.015(*). Displayed is a combined results of 3 independent experiments with n = 15 mice/group. c Mean tumor size (i) and survival (ii) of CT26 tumor-bearing mice receiving the indicated treatment combinations, with RT dose of 5 Gy × 5 consecutive fractions, and either anti-CD4 or anti-CD8α monoclonal antibodies to deplete CD4⁺ and CD8α⁺ cells prior to therapy. The legend key for each group is located next to the survival curve. NS = not significant, *p = 0.0448, **p = 0.0011. P-value was derived using the Wilcoxon test. N = 6 mice/group. Displayed is one representative experiment of 2 total experiments.