FIGURE 6.

Combination treatment with CP, anti‐PD‐1 antibody, and l‐arginine increases the number of cured mice. A, BALB/c mice were injected sc with CT26 cells (5 × 10⁵). On day 12 after tumor inoculation, mice received ip injection of CP (100 mg/kg) followed by ip injection of anti‐PD‐1 mAb (100 μg/mouse) on days 13 and 15. As a control, rat IgG was injected ip l‐arginine (30 mg/mouse) was orally administered daily from day 12. Dotted line indicates the untreated control. Numbers in parentheses are cured mice/total mice. B, Tumor size on day 33. C, At 1 mo after complete regression of sc inoculated CT26, CT26 cells (2.5 × 10⁵) were injected sc into the flank of mice. In some mice, either anti‐CD4 antibody, anti‐CD8 antibody, or control rat IgG was injected ip twice, 3 and 1 d before CT26 inoculation, at a dose of 150 µg. Similarly, naïve mice were inoculated sc with CT26 cells. Numbers in parentheses are rejected mice/total mice. D, The cell numbers of tumor tissues, the cell numbers and proportions of CD4⁺ T cells, CD8⁺ T cells and MDSCs were measured and counted. Data are means ± standard deviations of 4 mice. E, On day 26 after tumor inoculation, the plasma levels of l‐arginine and l‐tryptophan were measured by LC‐MS. Data are means ± standard deviations of 7 mice. *P < .05, **P < .01, n.s., not significant (ANOVA)