Systemic activation of the immune system after intravenous administration of R848 in EG7 tumor-bearing mice leads to increased survival. (A-B) Splenocytes were harvested at 2 and 4 hours, and T (A) and B (B) lymphocytes were analyzed for CD69 expression by flow cytometry. (C) Induction of systemic cytokine responses was measured in the plasma using multiplex assays. Experimental groups contained 5 mice. *P < .05 (2-tailed Student t test). **P < .01 (2-tailed Student t test). ***P < .001 (2-tailed Student t test). (D) Survival curve for EG7 tumor-bearing mice dosed intravenously with R848 either once or weekly. Experimental groups contained at least 7 mice and are representative of at least 2 independent experiments. *P < .05, compared with control mice (log-rank; Mantel-Cox test).