{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:29:23Z","timestamp":1772137763341,"version":"3.50.1"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,9,5]]},"abstract":"<jats:p>The activation NKG2D receptor has been shown to play an important role in the control of experimental tumor growth and metastases expressing ligands for NKG2D; however, a function for this recognition pathway in host protection from de novo tumorigenesis has never been demonstrated. We show that neutralization of NKG2D enhances the sensitivity of wild-type (WT) C57BL\/6 and BALB\/c mice to methylcholanthrene (MCA)-induced fibrosarcoma. The importance of the NKG2D pathway was additionally illustrated in mice deficient for either IFN-\u03b3 or tumor necrosis factor\u2013related apoptosis-inducing ligand, whereas mice depleted of natural killer cells, T cells, or deficient for perforin did not display any detectable NKG2D phenotype. Furthermore, IL-12 therapy preventing MCA-induced sarcoma formation was also largely dependent on the NKG2D pathway. Although NKG2D ligand expression was variable or absent on sarcomas emerging in WT mice, sarcomas derived from perforin-deficient mice were Rae-1+ and immunogenic when transferred into WT syngeneic mice. These findings suggest an important early role for the NKG2D in controlling and shaping tumor formation.<\/jats:p>","DOI":"10.1084\/jem.20050994","type":"journal-article","created":{"date-parts":[[2005,8,29]],"date-time":"2005-08-29T20:13:17Z","timestamp":1125346397000},"page":"583-588","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":273,"title":["NKG2D function protects the host from tumor initiation"],"prefix":"10.1084","volume":"202","author":[{"given":"Mark J.","family":"Smyth","sequence":"first","affiliation":[{"name":"1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}]},{"given":"Jeremy","family":"Swann","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}]},{"given":"Erika","family":"Cretney","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}]},{"given":"Nadeen","family":"Zerafa","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}]},{"given":"Wayne M.","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"2Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110"}]},{"given":"Yoshihiro","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"1Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia"}]}],"member":"291","published-online":{"date-parts":[[2005,8,29]]},"reference":[{"key":"2023072513174396600_BIB1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1084\/jem.173.4.1017","volume":"173","year":"1991","journal-title":"J. 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