{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:10:53Z","timestamp":1785345053183,"version":"3.55.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"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":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hepatocellular carcinoma (HCC) has the third highest cancer-related mortality rate globally. The immunosuppressive microenvironment of HCC limits effective treatment options. HCC cells and associated microenvironmental factors suppress NK and T cell infiltration and cytotoxic activities. The abnormal number or function of NK and T cells leads to a lack of immune surveillance. Recently, immunotherapy targeting PD-1 and PD-L1 has been shown to activate functionally exhausted cytotoxic immune cells in some solid tumors. However, the response rate and therapeutic efficacy against solid tumors with little lymphocyte infiltration are limited, especially for HCC. Therefore, new targets and therapeutics that induce tumor cell apoptosis and overcome the problem of depletion of immune cells, thereby inhibiting the immune escape of HCC cells, are urgently required. Butaselen (2-bis[2-(1,2-benzisothiazol-2(2H)-ketone)]butane), an organic molecule containing selenium, is a new type of thioredoxin reductase inhibitor. In this study, we found that butaselen promoted NK and T cell activity and infiltration in the tumor microenvironment in HCC-bearing mice by enhancing the expression of CXCR3, NKG2D, and their respective ligands. When used alone, it can significantly inhibit tumor growth and exert a synergistic effect in combination with PD-1 blockade. We suggested the role of the thioredoxin reductase system in the regulation of the tumor immunosuppressive microenvironment and developed a new effective therapeutic molecule for HCC, revealing the mechanism of butaselen in inhibiting tumor cell immune escape.<\/jats:p>","DOI":"10.4049\/jimmunol.2200389","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:37:31Z","timestamp":1672936651000},"page":"681-695","source":"Crossref","is-referenced-by-count":12,"title":["A Novel TrxR1 Inhibitor Regulates NK and CD8+ T Cell Infiltration and Cytotoxicity, Enhancing the Efficacy of Anti\u2013PD-1 Immunotherapy against Hepatocarcinoma"],"prefix":"10.1093","volume":"210","author":[{"given":"Xiaoxia","family":"Su","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Yin","sequence":"additional","affiliation":[{"name":"Shanghai Yuanxi Medicine Corp. , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"2025021008003497700_r1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"2025021008003497700_r2","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The tumor microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr. Biol."},{"key":"2025021008003497700_r3","doi-asserted-by":"crossref","first-page":"793343","DOI":"10.3389\/fimmu.2021.793343","article-title":"Epigenetic and immune-cell infiltration changes in the tumor microenvironment in hepatocellular carcinoma","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Immunol."},{"key":"2025021008003497700_r4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.semcancer.2021.02.015","article-title":"Cellular heterogeneity and plasticity in liver cancer","volume":"82","author":"Chan","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"2025021008003497700_r5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41392-020-0187-x","article-title":"The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects","volume":"5","author":"Tang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"2025021008003497700_r6","doi-asserted-by":"crossref","first-page":"662135","DOI":"10.3389\/fonc.2021.662135","article-title":"Tumor microenvironment alters chemoresistance of hepatocellular carcinoma through CYP3A4 metabolic activity","volume":"11","author":"\u00d6zkan","year":"2021","journal-title":"Front. Oncol."},{"key":"2025021008003497700_r7","first-page":"147","article-title":"CXCR4-guided liposomes regulating hypoxic and immunosuppressive microenvironment for sorafenib-resistant tumor treatment","volume":"17","author":"Wang","year":"2022","journal-title":"Bioact. Mater."},{"key":"2025021008003497700_r8","doi-asserted-by":"crossref","first-page":"E5900","DOI":"10.1073\/pnas.1706559114","article-title":"Delineation of an immunosuppressive gradient in hepatocellular carcinoma using high-dimensional proteomic and transcriptomic analyses","volume":"114","author":"Chew","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008003497700_r9","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1136\/gutjnl-2018-316510","article-title":"Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma","volume":"68","author":"Lim","year":"2019","journal-title":"Gut"},{"key":"2025021008003497700_r10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/cmi.2014.91","article-title":"NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma","volume":"12","author":"Sun","year":"2015","journal-title":"Cell. Mol. Immunol."},{"key":"2025021008003497700_r11","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1038\/s41467-021-21804-1","article-title":"Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma","volume":"12","author":"Hung","year":"2021","journal-title":"Nat. Commun."},{"key":"2025021008003497700_r12","doi-asserted-by":"crossref","first-page":"e1477459","DOI":"10.1080\/2162402X.2018.1477459","article-title":"Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment","volume":"7","author":"Wu","year":"2018","journal-title":"OncoImmunology"},{"key":"2025021008003497700_r13","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1038\/onc.2017.209","article-title":"Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers","volume":"36","author":"Liu","year":"2017","journal-title":"Oncogene"},{"key":"2025021008003497700_r14","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1053\/j.gastro.2017.06.017","article-title":"Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas","volume":"153","author":"Zhou","year":"2017","journal-title":"Gastroenterology"},{"key":"2025021008003497700_r15","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"2025021008003497700_r16","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol."},{"key":"2025021008003497700_r17","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"2025021008003497700_r18","doi-asserted-by":"crossref","first-page":"eaav7816","DOI":"10.1126\/scitranslmed.aav7816","article-title":"Sensitization to immune checkpoint blockade through activation of a STAT1\/NK axis in the tumor microenvironment","volume":"11","author":"Zemek","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2025021008003497700_r19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ccell.2016.02.004","article-title":"Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. [Published erratum appears in 2016 Cancer Cell 30: 500.]","volume":"29","author":"Tang","year":"2016","journal-title":"Cancer Cell"},{"key":"2025021008003497700_r20","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1172\/JCI133055","article-title":"A tumor-intrinsic PD-L1\/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy","volume":"130","author":"Theivanthiran","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2025021008003497700_r21","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature14011","article-title":"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients","volume":"515","author":"Herbst","year":"2014","journal-title":"Nature"},{"key":"2025021008003497700_r22","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3-related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2025021008003497700_r23","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3389\/fimmu.2020.00223","article-title":"Sensitizing the tumor microenvironment to immune checkpoint therapy","volume":"11","author":"Zemek","year":"2020","journal-title":"Front. Immunol."},{"key":"2025021008003497700_r24","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3389\/fimmu.2018.01009","article-title":"IL-15 overcomes hepatocellular carcinoma-induced NK cell dysfunction","volume":"9","author":"Easom","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008003497700_r25","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1002\/hep.30235","article-title":"Deficient natural killer cell NKp30-mediated function and altered NCR3 splice variants in hepatocellular carcinoma","volume":"69","author":"Mantovani","year":"2019","journal-title":"Hepatology"},{"key":"2025021008003497700_r26","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3390\/cancers12030627","article-title":"Impaired anti-tumor T cell response in hepatocellular carcinoma","volume":"12","author":"Chaoul","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2025021008003497700_r27","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.tips.2017.06.001","article-title":"Targeting the thioredoxin system for cancer therapy","volume":"38","author":"Zhang","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"2025021008003497700_r28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10620-018-5307-x","article-title":"Clinical significance of the thioredoxin system and thioredoxin-domain-containing protein family in hepatocellular carcinoma","volume":"64","author":"Cho","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"2025021008003497700_r29","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1002\/hep.30467","article-title":"Induction of oxidative stress through inhibition of thioredoxin reductase 1 is an effective therapeutic approach for hepatocellular carcinoma","volume":"69","author":"Lee","year":"2019","journal-title":"Hepatology"},{"key":"2025021008003497700_r30","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3389\/fphar.2019.01180","article-title":"Piperlongumine, a novel TrxR1 inhibitor, induces apoptosis in hepatocellular carcinoma cells by ROS-mediated ER stress. [Published erratum appears in 2022 Front. Pharmacol. 13: 806724.]","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"2025021008003497700_r31","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3390\/antiox8100501","article-title":"Thioredoxin downregulation enhances sorafenib effects in hepatocarcinoma cells","volume":"8","author":"L\u00f3pez-Grueso","year":"2019","journal-title":"Antioxidants"},{"key":"2025021008003497700_r32","doi-asserted-by":"crossref","first-page":"100785","DOI":"10.1016\/j.tranon.2020.100785","article-title":"Redox modulation and induction of ferroptosis as a new therapeutic strategy in hepatocellular carcinoma","volume":"13","author":"Lippmann","year":"2020","journal-title":"Transl. Oncol."},{"key":"2025021008003497700_r33","doi-asserted-by":"crossref","first-page":"101949","DOI":"10.1016\/j.redox.2021.101949","article-title":"Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer","volume":"42","author":"Freire Boullosa","year":"2021","journal-title":"Redox Biol."},{"key":"2025021008003497700_r34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/ijc.32410","article-title":"Therapeutic cooperation between auranofin, a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer","volume":"146","author":"Raninga","year":"2020","journal-title":"Int. J. Cancer"},{"key":"2025021008003497700_r35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.redox.2017.09.014","article-title":"Butaselen prevents hepatocarcinogenesis and progression through inhibiting thioredoxin reductase activity. [Published erratum appears in 2020 Redox Biol. 32: 101526.]","volume":"14","author":"Zheng","year":"2018","journal-title":"Redox Biol."},{"key":"2025021008003497700_r36","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1038\/s41467-022-30543-w","article-title":"Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis","volume":"13","author":"Guan","year":"2022","journal-title":"Nat. Commun."},{"key":"2025021008003497700_r37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cbi.2017.07.020","article-title":"Synergism between thioredoxin reductase inhibitor ethaselen and sodium selenite in inhibiting proliferation and inducing death of human non-small cell lung cancer cells","volume":"275","author":"Zheng","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"2025021008003497700_r38","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.ymthe.2022.01.018","article-title":"The antitumoral activity of TLR7 ligands is corrupted by the microenvironment of pancreatic tumors","volume":"30","author":"Rouanet","year":"2022","journal-title":"Mol. Ther."},{"key":"2025021008003497700_r39","doi-asserted-by":"crossref","first-page":"e000847","DOI":"10.1136\/jitc-2020-000847","article-title":"CDK4\/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy","volume":"8","author":"Lai","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"2025021008003497700_r40","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"issue":"W1","key":"2025021008003497700_r41","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2025021008003497700_r42","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.freeradbiomed.2016.08.028","article-title":"Serum thioredoxin reductase is highly increased in mice with hepatocellular carcinoma and its activity is restrained by several mechanisms","volume":"99","author":"Zhang","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"2025021008003497700_r43","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41417-021-00303-x","article-title":"Key chemokines direct migration of immune cells in solid tumors","volume":"29","author":"Kohli","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"2025021008003497700_r44","doi-asserted-by":"crossref","first-page":"11067","DOI":"10.1021\/acsnano.9b10103","article-title":"Boosting natural killer cell-based cancer immunotherapy with selenocystine\/transforming growth factor-beta inhibitor-encapsulated nanoemulsion","volume":"14","author":"Liu","year":"2020","journal-title":"ACS Nano"},{"key":"2025021008003497700_r45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40364-021-00350-4","article-title":"Recent advances in systemic therapy for hepatocellular carcinoma","volume":"10","author":"Zhang","year":"2022","journal-title":"Biomark. Res."},{"key":"2025021008003497700_r46","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.3390\/cells10061332","article-title":"Natural killer cells and T cells in hepatocellular carcinoma and viral hepatitis: current status and perspectives for future immunotherapeutic approaches","volume":"10","author":"Kalathil","year":"2021","journal-title":"Cells"},{"key":"2025021008003497700_r47","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S1470-2045(21)00333-8","article-title":"Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis","volume":"22","author":"Zhou","year":"2021","journal-title":"Lancet Oncol."},{"key":"2025021008003497700_r48","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.immuni.2019.04.010","article-title":"Intratumoral activity of the CXCR3 chemokine system is required for the efficacy of anti-PD-1 therapy","volume":"50","author":"Chow","year":"2019","journal-title":"Immunity"},{"key":"2025021008003497700_r49","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1084\/jem.20181454","article-title":"NK cells switch from granzyme B to death receptor-mediated cytotoxicity during serial killing","volume":"216","author":"Prager","year":"2019","journal-title":"J. Exp. Med."},{"key":"2025021008003497700_r50","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jhep.2011.07.008","article-title":"NKG2D and its ligands: key to immunotherapy of liver cancer?","volume":"56","author":"Mondelli","year":"2012","journal-title":"J. Hepatol."},{"key":"2025021008003497700_r51","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3389\/fimmu.2019.00661","article-title":"NKG2D\/NKG2-ligand pathway offers new opportunities in cancer treatment","volume":"10","author":"Frazao","year":"2019","journal-title":"Front. Immunol."},{"key":"2025021008003497700_r52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s12072-018-9909-3","article-title":"Activity of IL-12\/15\/18 primed natural killer cells against hepatocellular carcinoma","volume":"13","author":"Zhuang","year":"2019","journal-title":"Hepatol. Int."},{"key":"2025021008003497700_r53","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.chembiol.2019.04.003","article-title":"Parvifoline AA Promotes Susceptibility of Hepatocarcinoma to Natural Killer Cell-Mediated Cytolysis by Targeting Peroxiredoxin","volume":"26","author":"Zhu","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"2025021008003497700_r54","doi-asserted-by":"crossref","first-page":"E3509","DOI":"10.1073\/pnas.1802691115","article-title":"Inhibition of enhancer of zeste homolog 2 (EZH2) induces natural killer cell-mediated eradication of hepatocellular carcinoma cells","volume":"115","author":"Bugide","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008003497700_r55","doi-asserted-by":"crossref","first-page":"E761","DOI":"10.1073\/pnas.1620433114","article-title":"Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity","volume":"114","author":"Chamoto","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008003497700_r56","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.3390\/cancers12071748","article-title":"Reactive oxygen species and antitumor immunity-from surveillance to evasion","volume":"12","author":"Kotsafti","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2025021008003497700_r57","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13045-022-01242-2","article-title":"Improvement of the anticancer efficacy of PD-1\/PD-L1 blockade via combination therapy and PD-L1 regulation","volume":"15","author":"Wu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"2025021008003497700_r58","doi-asserted-by":"crossref","first-page":"eabd2712","DOI":"10.1126\/sciadv.abd2712","article-title":"Revisiting the PD-1 pathway","volume":"6","author":"Patsoukis","year":"2020","journal-title":"Sci. Adv."},{"key":"2025021008003497700_r59","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.freeradbiomed.2018.05.001","article-title":"Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment","volume":"127","author":"Gandin","year":"2018","journal-title":"Free Radic. Biol. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/5\/681\/61469925\/ji2200389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/5\/681\/61469925\/ji2200389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T08:02:58Z","timestamp":1739174578000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/210\/5\/681\/7932654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":59,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2200389","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3]]},"published":{"date-parts":[[2023,1,4]]}}}