Antitumor activity of agonist CD40 mAb in KPC mice is T cell–independent. (A) KPC mice were treated with gemcitabine or phosphate-buffered saline (PBS) on day 0 and day 7, with control IgG2a or FGK45 administered on day 2. Cohorts of KPC mice receiving treatment with FGK45 were also depleted of CD4+ or CD8+ cells or both CD4+ and CD8+ cells with the use of GK1.5 and 2.43 antibodies, respectively, on days −1, 0, 1, 3, 7, and 10. Percent change in tumor volume from day −1 (baseline) to day +14 is shown for each mouse as a waterfall plot (in comparison with PBS + IgG2a, gemcitabine + FGK45: P < 0.05; gemcitabine + IgG2a: P = 1.00; PBS + FGK45: P < 0.05; FGK45 + GK1.5: P < 0.05; FGK + 2.43: P < 0.05; FGK45 + GK1.5 + 2.43: P < 0.05; Fisher’s exact test). Hematoxylin and eosin (H&E) histology [(B) to (E)] and CD3 immunohistochemistry [(F) to (I)] are shown for tumors from KPC mice treated with IgG2a (B and F) or FGK45 (C to E and G to I). Responders (D), (E), (H), and (I) were defined as FGK45-treated mice that demonstrated tumor regression by ultrasound analysis. FGK45-treated mice with tumor progression by ultrasound were defined as nonresponders (C) and (G). Scale bars, 50 μm.