Fig. 4

Tumor growth and immune infiltrates in vivo. C57BL/6 mice were infected 2 days after birth (P2) with mCMV (mCMV+). Orthotopic tumors (luciferase-expressing GL261Luc2) were stereotactically implanted at least 15 weeks after infection. The expression of immediate early gene (IE-1) was detected in the brain of mCMV + animals, but not in mCMV naïve. Transcripts of both the immediate early IE-1 and the envelope-associated glycoprotein B (gB) (not shown) were not detected prior to tumor cell injection, then increased during tumor growth. Bioluminescence imaging (BLI) and T2-weighted magnetic resonance imaging (MRI) revealed significantly faster tumor growth in mCMV + mice than in controls (A). Larger tumor volumes lead to earlier weight loss and shorter survival in mCMV + mice. (p < 0.001) (B) Effect of mCMV dependent on initial tumor mass with mechanisms of immune evasion might become predominant over the rapid proliferation and consecutive mass effect in primarily larger tumors (C). t-distributed stochastic neighbor embedding (tSNE) plot of immune infiltrates in tumors from mCMV + mice. (D) Tumors of mCMV + mice are characterized by higher numbers of B cell infiltrates (p = 0.0197) and lower levels of NK cell infiltration (p = 0.0027) compared to uninfected controls (E). mCMV leads to the infiltration of mCMV specific CTLs and dendritic cells (p = 0.0196) (F).