| First Author | Wilski NA | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 11 | Pages | 2961-2972 |
| PubMed ID | 32284333 | Mgi Jnum | J:337104 |
| Mgi Id | MGI:6432275 | Doi | 10.4049/jimmunol.1901136 |
| Citation | Wilski NA, et al. (2020) STING Sensing of Murine Cytomegalovirus Alters the Tumor Microenvironment to Promote Antitumor Immunity. J Immunol 204(11):2961-2972 |
| abstractText | 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. |
