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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.<\/jats:p>","DOI":"10.4049\/jimmunol.1901136","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T19:40:56Z","timestamp":1586806856000},"page":"2961-2972","source":"Crossref","is-referenced-by-count":12,"title":["STING Sensing of Murine Cytomegalovirus Alters the Tumor Microenvironment to Promote Antitumor Immunity"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0285-0853","authenticated-orcid":false,"given":"Nicole A","family":"Wilski","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-0753","authenticated-orcid":false,"given":"Colby","family":"Stotesbury","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Del Casale","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1969-2911","authenticated-orcid":false,"given":"Brian","family":"Montoya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6642-5472","authenticated-orcid":false,"given":"Luis J","family":"Sigal","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-7198","authenticated-orcid":false,"given":"Christopher M","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"2025030417511950900_r1","doi-asserted-by":"crossref","first-page":"37513","DOI":"10.18632\/oncotarget.7038","article-title":"Salmonella inhibits tumor angiogenesis by downregulation of vascular endothelial growth factor","volume":"7","author":"Tu","year":"2016","journal-title":"Oncotarget"},{"key":"2025030417511950900_r2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2217\/imt-2017-0188","article-title":"TLR7 agonist in combination with Salmonella as an effective antimelanoma immunotherapy","volume":"10","author":"Vola","year":"2018","journal-title":"Immunotherapy"},{"key":"2025030417511950900_r3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1158\/2326-6066.CIR-14-0216","article-title":"Virotherapy with a Semliki forest virus-based vector encoding IL12 synergizes with PD-1\/PD-L1 blockade","volume":"3","author":"Quetglas","year":"2015","journal-title":"Cancer Immunol. 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