Prophylactic TLR9 stimulation reduces brain metastasis through microglia activation.

We focused on the first 24 hours of tumor colonization in the brain, for the following reasons: (i) a single administration of CpG-C, which we herein found effective, is known to exert immune activation within hours and for up to 72 hours [ 11 ]; (ii) bioluminescence imaging indicated a nonsignificant trend for beneficial effects a day following tumor inoculation ( S1 Fig ); and (iii) tumor cells successfully proliferate to macrometastases only if they extravasate into the brain parenchyma within the first three days [ 46 ].

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