STING in tumor and host cells cooperatively work for NK cell-mediated tumor growth retardation.
An interferon-inducing DNA sensor STING participates in tumor rejection in mouse models. Here we examined what mechanisms contribute to STING-dependent growth retardation of B16 melanoma sublines by NK cells in vivo. The studies were designed using WT and STING KO black mice, and B16D8 (an NK-sensitive melanoma line having STING) and STING KO B16D8 sublines established for this study. The results from tumor-implant studies suggested that STING in host immune cells and tumor cells induced distinct profiles of chemokines including CXCL10, CCL5 and IL-33, and both participated in NK cell infiltration and activation in B16D8 tumor. Spontaneous activation of STING occurs in host-immune and tumor cells of this NK-sensitive tumor, thereby B16D8 tumor growth being suppressed in this model. Our data show that STING induces tumor cytotoxicity by NK cells through tumor and host immune cell network to contribute to innate surveillance and suppression of tumors in vivo.
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Ken
K
Takashima
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Yohei
Y
Takeda
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Hiroyuki
H
Oshiumi
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Hiroaki
H
Shime
Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
Masaru
M
Okabe
Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
Masahito
M
Ikawa
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Misako
M
Matsumoto
Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan. Electronic address: seya-tu@pop.med.hokudai.ac.jp.
Tsukasa
T
Seya
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics*; D000099197:STING Protein
D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D016899:Interferon-beta; D000067596:Interleukin-33; D008565:Membrane Proteins; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein
Antitumor immunity; B16 cell line; Interferon; NK cells; STING