{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:19:47Z","timestamp":1773062387012,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502450"],"award-info":[{"award-number":["81502450"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to investigate the synergistic effect of\u00a0octamer\u2010binding transcription factor 4 and sex determining region Y\u2010box 2 (OCT4&amp;SOX2)\u2010specific cytotoxic T lymphocytes (CTLs) and programmed cell death protein\u00a01 (PD\u20101) inhibitor on killing lung cancer stem\u2010like cells (LCSCs) and their efficacy in treating drug\u2010resistant lung cancer (DRLC) mice. OCT4&amp;SOX2\u2010specific CTLs and PD\u20101 inhibitor with differed doses were applied to treat PC9 cells and PC9 LCSCs. Cell counting kit\u20108 (CCK8) assay and flow cytometry (FCM) assay with carboxyfluorescein diacetate\/succinimidyl ester staining target cells before treatment and propidium iodide (PI) staining dead cells after treatment were conducted to detect the cytotoxic activity. DRLC mice were constructed by injection of PC9 LCSCs suspension and Matrigel into left lung of SD mice. DRLC mice were randomly divided into five groups: control group, cytomegalovirus (CMV) pp65 CTLs group, OCT4&amp;SOX2 CTLs group, PD\u20101 inhibitor group, and OCT4&amp;SOX2 CTLs\u2009+\u2009PD\u20101 inhibitor group. In vitro, both CCK8 assay and FCM assay disclosed that OCT4&amp;SOX2\u2010specific CTLs plus PD\u20101 inhibitor presented with elevated cytotoxic activity on PC9 cells and PC9 LCSCs. In vivo, tumor volume and tumor weight were decreased, while tumor necrosis and tumor apoptosis were increased in OCT4&amp;SOX2 CTLs group than CMV pp65 CTLs group and control group, and in OCT4&amp;SOX2 CTLs\u2009+\u2009PD\u20101 inhibitor group than OCT4&amp;SOX2 CTLs group and PD\u20101 inhibitor group. In addition, CD8 expression was increased while OCT4&amp;SOX2 expressions were decreased in OCT4&amp;SOX2 CTLs\u2009+\u2009PD\u20101 inhibitor group than OCT4&amp;SOX2 CTLs group and PD\u20101 inhibitor group. In conclusion, OCT4&amp;SOX2\u2010specific CTLs and PD\u20101 inhibitor presented with the synergistic effect on killing LCSCs in vitro and treating DRLC mice in vivo.<\/jats:p>","DOI":"10.1002\/jcp.27423","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T10:44:46Z","timestamp":1541069086000},"page":"6758-6768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["OCT4&amp;SOX2\u2010specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem\u2010like cells in vitro and treating drug\u2010resistant lung cancer mice in vivo"],"prefix":"10.1002","volume":"234","author":[{"given":"Xueyan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyu","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianlin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-3771","authenticated-orcid":false,"given":"Baohui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3932"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.11.1977"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21775"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.07.001"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80011"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001775"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915174107"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2675"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.1089.65.3"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30958-8"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31473-8"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh194"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192461099"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32446"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.3019"},{"issue":"1","key":"e_1_2_7_1_17_1","first-page":"A52","article-title":"Immunotargeting of cancer stem cells","volume":"19","author":"Kwiatkowska\u2010Borowczyk E. 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