{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:31Z","timestamp":1787030851858,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"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":[[2018,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cancer-initiating\/sustaining stem cell subsets (CSCs) have the potential to regenerate cancer cell populations and are resistant to routine therapeutic strategies, thus attracting much attention in anticancer research. In this study, an innovative framework of endogenous microenvironment-renewal for addressing such a dilemma has been just developed. CSCs in three-dimensional multipotent spheroid-engineered biologics were prepared with 150 Gy radiation and inoculated into 15-mo-old BALB\/c and C57BL\/6 mice bearing diverse advanced tumors covering Mammary 4T1, liver Hepa, lung LL\/2, and colon C26 tumors and distant metastases. Subsequently, the systematic microenvironment of tumor-bearing hosts was rapidly remodeled to resettle thymic cortex and medulla rudiment as an endogenous foxn1-thymosin reprogramming TCR-repertoire for resetting MHC-unrestricted multifunction renewal. Postrenewal V\u03b34\u03b3\u03b4T-subsets would bind and lead migrating CSCs into apoptosis. Moreover, TCR repertoire multifunction renewal could reverse tumor metastases from tumoricidal resistance into eventual regression as a blockade of cancer-sustaining Bmi-1\/Nanog-Oct4-Sox2 renewal loop with sequent multivalent depletion of both migrating\/in situ CSCs and non\u2013stem terminal cancer cell subsets. This study represents a promising start to set up a generalizable strategy of three-dimensional biologics evoking an endogenous integral microenvironment into pluripotent renewal versus advanced cancer.<\/jats:p>","DOI":"10.4049\/jimmunol.1701727","type":"journal-article","created":{"date-parts":[[2018,8,27]],"date-time":"2018-08-27T11:47:30Z","timestamp":1535370450000},"page":"1975-1983","source":"Crossref","is-referenced-by-count":7,"title":["Three-Dimensional Ameliorated Biologics Elicit Thymic Renewal in Tumor-Bearing Hosts"],"prefix":"10.1093","volume":"201","author":[{"given":"Yanna","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, West China Hospital\/Second Hospital, Sichuan University, High Technological Development Zone , Chengdu, Sichuan 610041 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiancheng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy\/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University , Chengdu 610041 ,","place":["People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,10,1]]},"reference":[{"key":"2025030417573024500_r1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrc3298","article-title":"Evolutionary dynamics of carcinogenesis and why targeted therapy does not work","volume":"12","author":"Gillies","year":"2012","journal-title":"Nat. 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