Figure 5.

Blocking mast cell function improves the anti-tumor efficacy of anti-OX40 in both syngeneic allograft and autochthonous KPC model

(A) Experimental design and (B) survival curves of KPC-GEMM mice. Combination therapy with anti-OX40 and cromolyn significantly extended survival in KPC mice compared with control (p = 0.0007); anti-OX40 alone had no survival benefit (p = 0.1318); cromolyn significantly increased survival (p = 0.0388); and combination therapy with anti-OX40 and cromolyn resulted in longer survival than did cromolyn alone (p = 0.0435).

(C–F) Immunohistochemical analysis of CD8 infiltration (C and D) and granzyme B expression (E and F) showed little infiltration of effector T cells into the tumor microenvironment in control mice (black sets in C–F) and after treatment with cromolyn (green sets in C–F), slightly increased with the treatment with anti-OX40 (blue sets in C–F), however, a dramatic increase was found in mice treated with agonist anti-OX40 and cromolyn (red sets in C–F).

(D and F) Quantification of CD8 and granzyme B positive cells—average from 5 representative high-power fields. A one-way ANOVA, followed by the Fisher’s least significant difference (LSD) multiple comparison test, shows the significances by ∗: p < 0.05; ∗∗: p < 0.01; ∗∗∗: p < 0.001; ∗∗∗∗: p < 0.0001.