Journal
JOURNAL OF IMMUNOLOGY
Volume 204, Issue 11, Pages 2961-2972Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1901136
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Funding
- American Cancer Society [RSG-15184-01]
- Pennsylvania Department of Health Research formula funds [SAP 4100072566]
- National Institutes of Health (NIH)/National Institute on Aging [RO1 AG048602]
- NIH/National Institute of Allergy and Infectious Diseases (NIAID) [AI110457, AI065544]
- NIH/NIAID [F32AI129352, T32 AI134646]
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CMV has been proposed to play a role in cancer progression and invasiveness. However, CMV has been increasingly studied as a cancer vaccine vector, and multiple groups, including ours, have reported that the virus can drive antitumor immunity in certain models. Our previous work revealed that intratumoral injections of wild-type murine CMV (MCMV) into B16-F0 melanomas caused tumor growth delay in part by using a viral chemokine to recruit macrophages that were subsequently infected. We now show that MCMV acts as a STING agonist in the tumor. MCMV infection of tumors in STING-deficient mice resulted in normal recruitment of macrophages to the tumor, but poor recruitment of CD8(+) T cells, reduced production of inflammatory cytokines and chemokines, and no delay in tumor growth. In vitro, expression of type I IFN was dependent on both STING and the type I IFNR. Moreover, type I IFN alone was sufficient to induce cytokine and chemokine production by macrophages and B16 tumor cells, suggesting that the major role for STING activation was to produce type I IFN. Critically, viral infection of wild-type macrophages alone was sufficient to restore tumor growth delay in STING-deficient animals. Overall, these data show that MCMV infection and sensing in tumor-associated macrophages through STING signaling is sufficient to promote antitumor immune responses in the B16-F0 melanoma model.
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