{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:25:35Z","timestamp":1785291935863,"version":"3.55.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of \u03b1-galactosylceramide (\u03b1-GalCer) in animals enhances antitumor immunity via activation of the invariant NKT (iNKT) cells. However, repeated injections of \u03b1-GalCer result in long-term unresponsiveness or anergy of iNKT cells, severely limiting its efficacy in tumor eradication. The mechanisms leading to iNKT cell anergy remain poorly understood. We report in this study that the tuberous sclerosis 1 (TSC1), a negative regulator of mTOR signaling, plays a crucial role in iNKT cell anergy. Deficiency of TSC1 in iNKT cells results in resistance to \u03b1-GalCer\u2013induced anergy, manifested by increased expansion of and cytokine production by iNKT cells in response to secondary Ag stimulation. It is correlated with impaired upregulation of programmed death-1, Egr2, and Grail. Moreover, TSC1-deficient iNKT cells display enhanced antitumor immunity in a melanoma lung metastasis model. Our data suggest targeting TSC1\/2 as a strategy for boosting antitumor immune therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1302076","type":"journal-article","created":{"date-parts":[[2014,2,15]],"date-time":"2014-02-15T02:01:49Z","timestamp":1392429709000},"page":"2643-2650","source":"Crossref","is-referenced-by-count":27,"title":["Tuberous Sclerosis 1 Promotes Invariant NKT Cell Anergy and Inhibits Invariant NKT Cell\u2013Mediated Antitumor Immunity"],"prefix":"10.1093","volume":"192","author":[{"given":"Jinhong","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center , Durham, NC 27710"},{"name":"Division of Pediatric Pulmonology, Department of Internal Medicine, Shanghai Children\u2019s Medical Center affiliated with Shanghai Jiaotong University School of Medicine , Shanghai 200127,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwook","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danli","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center , Durham, NC 27710"},{"name":"School of Laboratory Medicine, Wenzhou Medical University , Wenzhou, Zhejiang 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center , Durham, NC 27710"},{"name":"Laboratory Medicine Center, Nanfang Hospital, Southern Medical University , Guangzhou, Guangdong 510515,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine, Wenzhou Medical University , Wenzhou, Zhejiang 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,3,15]]},"reference":[{"key":"2025032404184873600_r1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.immunol.25.022106.141711","article-title":"The biology of NKT cells","volume":"25","author":"Bendelac","year":"2007","journal-title":"Annu. 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