title: VSIG4 expression on macrophages facilitates lung cancer development.
abstract: Tumor-associated macrophages are a prominent component of lung cancer stroma and contribute to tumor progression. The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage protein that has the capacity to inhibit T-cell activation, has a potential role in the development of lung cancer. In this study, 10 human non-small-cell lung cancer specimens were collected and immunohistochemically analyzed for VSIG4 expression. Results showed massive VSIG4(+) cell infiltration throughout the samples. Immunofluorescent double staining showed that VSIG4 was present on CD68(+) macrophages, but absent from CD3(+) T cells, CD31(+) endothelial cells, and CK-18(+) epithelial cells. Moreover, VSIG4 was coexpressed on B7-H1(+) and B7-H3(+) cells in these tumor specimens. Transfection of the VSIG4 gene into 293FT cells demonstrated that the VSIG4 signal could inhibit cocultured CD4(+) and CD8(+) T-cell proliferation and cytokine (IL-2 and IFN-γ) production in vitro. Interestingly, in a murine tumor model induced by Lewis lung carcinoma cell line, we found that tumors grown in VSIG4-deficient (VSIG4(-/-)) mice were significantly smaller than those found in wild-type littermates. All of these results demonstrate that macrophage-associated VSIG4 is an activator that facilitates lung carcinoma development. Specific targeting of VSIG4 may prove to be a novel, efficacious strategy for the treatment of this carcinoma.
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Dayan
authors.initials: D
authors.lastname: Cao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Chengying
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fei
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.affiliation: Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ruan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D060887:B7 Antigens / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D060887:B7 Antigens; D060890:B7-H1 Antigen; D007371:Interferon-gamma; D007376:Interleukin-2; D011951:Receptors, Complement; C423236:CD274 protein, human; C423237:CD276 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C414427:VSIG4 protein, human