Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors

Table 1 Effect of TLR agonists on gene regulation in the tumor microenvironment

	Mean fold-change in mRNA levels (vs PBS treated controls)
Gene	CpG ODN + 3M control	3M-052 + CpG control	CpG ODN + 3M-052
IL-12	2.23* ± 0.18	1.40 ± 0.19	3.39*** ± 0.11
INFγ	1.94* ± 0.15	1.87* ± 0.25	2.81** ± 0.24
Granzyme B	1.69* ± 0.07	1.87* ± 0.08	4.44*** ± 0.23
Arg1	1.01 ± 0.09	0.63* ± 0.09	0.43** ± 0.08
Nos2	1.83 ± 0.05	0.39** ± 0.04	0.09** ± 0.04
CTLA-4	0.85* ± 0.03	0.52** ± 0.01	0.33*** ± 0.02
TGFβ	0.43* ± 0.03	0.45* ± 0.01	0.26** ± 0.02

Mice were treated as described in Figure 1. mRNA was isolated from tumor infiltrating cells one day after the second treatment and analyzed by RT-PCR. Each point represents the mean ± SD fold difference in cells from treated vs untreated tumor bearing mice derived from independently studying 6 mice/group in 2 independent experiments.
*, p < 0.05; **, p <0.01, ***, p <0.001 when compared to PBS treated controls. Note: the level of expression of all genes from mice treated with CpG ODN plus 3M-052 was also significantly different (p < .01 - 0.05) from that of mice treated with CpG ODN alone or 3M-052 alone.