{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:15:45Z","timestamp":1790180145520,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"40","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,10,6]]},"abstract":"<jats:p>\n                    The identification of individuals genetically susceptible to cancer calls for preventive measures to minimize the cancer risk in these high-risk populations. Immune prevention is made necessary by the anticipated health threat, but lack of enough high-affinity T cells against tumor-associated antigens and the unpredictability of tumor antigens make antigen-based immune prevention untenable for cancer. To address this issue, we explored a non-antigen-based cancer immune prevention strategy using the transgenic adenocarcinoma of mouse prostate model that spontaneously develops prostate cancer with 100% penetrance. We show that targeted mutation of the lymphotoxin \u03b1 (\n                    <jats:italic>LT<\/jats:italic>\n                    \u03b1) gene efficiently rescued tumor-reactive T cells, drastically reduced cancer incidence, and almost completely ablated metastasis. Remarkably, short-term treatments with the fusion protein consisting of constant region of IgG and extracellular domain of lymphotoxin \u03b2 receptor (LT\u03b2RIg) interrupted clonal deletion, reduced the size of the primary cancer, and completely prevented metastasis later in life. Our data demonstrated the value of non-antigen-based immune prevention for those with a genetic predisposition to cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0905707106","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T22:40:49Z","timestamp":1253745649000},"page":"17134-17139","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Targeting lymphotoxin-mediated negative selection to prevent prostate cancer in mice with genetic predisposition"],"prefix":"10.1073","volume":"106","author":[{"given":"Penghui","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Immunotherapy, Departments of Surgery, Internal Medicine, and Pathology, University of Michigan School of Medicine and Cancer Center, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"McNally","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Departments of Surgery, Internal Medicine, and Pathology, University of Michigan School of Medicine and Cancer Center, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago School of Medicine, Chicago, IL 60636"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago School of Medicine, Chicago, IL 60636"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Xin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago School of Medicine, Chicago, IL 60636"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Departments of Surgery, Internal Medicine, and Pathology, University of Michigan School of Medicine and Cancer Center, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Departments of Surgery, Internal Medicine, and Pathology, University of Michigan School of Medicine and Cancer Center, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Immunotherapy, Departments of Surgery, Internal Medicine, and Pathology, University of Michigan School of Medicine and Cancer Center, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,10,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81333-1"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/315115a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1978757"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(81)90021-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1651563"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/513891"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91578-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/301749"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200102)9999:9999<::AID-IJC1147>3.0.CO;2-C"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.52.1.371"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1808"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1999"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2098"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2015"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0507-579"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2022"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.5260"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.002005"},{"key":"e_1_3_3_20_2","first-page":"769","article-title":"Immunity to methylcholanthrene-induced sarcomas","volume":"18","author":"Prehn RT","year":"1957","unstructured":"RT Prehn, JM Main, Immunity to methylcholanthrene-induced sarcomas. 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