{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:41:28Z","timestamp":1792550488357,"version":"4.5.0"},"reference-count":70,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"695","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,5,10]]},"abstract":"<jats:p>\n            Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3\/\n            <jats:italic>CD276<\/jats:italic>\n            ) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3\u2019s role in cancer progression, predictive biomarkers for B7-H3\u2013targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing\n            <jats:italic>PTEN<\/jats:italic>\n            and\n            <jats:italic>TP53<\/jats:italic>\n            genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in\n            <jats:italic>PTEN\/TP53-<\/jats:italic>\n            deficient prostate cancer. We found that loss of\n            <jats:italic>PTEN<\/jats:italic>\n            and\n            <jats:italic>TP53<\/jats:italic>\n            induced B7-H3 expression by activating transcriptional factor Sp1. Prostate-specific deletion of\n            <jats:italic>Cd276<\/jats:italic>\n            resulted in delayed tumor progression and reversed the suppression of tumor-infiltrating T cells and NK cells in\n            <jats:italic>Pten\/Trp53<\/jats:italic>\n            genetically engineered mouse models. Furthermore, we tested the efficacy of the B7-H3 inhibitor in preclinical models of castration-resistant prostate cancer (CRPC). We demonstrated that enriched regulatory T cells and elevated programmed cell death ligand 1 (PD-L1) in myeloid cells hinder the therapeutic efficacy of B7-H3 inhibition in prostate tumors. Last, we showed that B7-H3 inhibition combined with blockade of PD-L1 or cytotoxic T lymphocyte\u2013associated protein 4 (CTLA-4) achieved durable antitumor effects and had curative potential in a\n            <jats:italic>PTEN\/TP53<\/jats:italic>\n            -deficient CRPC model. Given that B7-H3\u2013targeted therapies have been evaluated in early clinical trials, our studies provide insights into the potential of biomarker-driven combinatorial immunotherapy targeting B7-H3 in prostate cancer, among other malignancies.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adf6724","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T17:59:48Z","timestamp":1683741588000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":80,"title":["Immune checkpoint B7-H3 is a therapeutic vulnerability in prostate cancer harboring PTEN and TP53 deficiencies"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2236-4708","authenticated-orcid":true,"given":"Wei","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-1353","authenticated-orcid":true,"given":"Yin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Jimin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."},{"name":"Department of Biology, Colby College, Waterville, ME 04901, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6786-0705","authenticated-orcid":true,"given":"Haoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenling","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan H.","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"Van","sequence":"additional","affiliation":[{"name":"Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Leo","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."},{"name":"University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6246-0374","authenticated-orcid":true,"given":"Brad","family":"St.\u00a0Croix","sequence":"additional","affiliation":[{"name":"Tumor Angiogenesis Unit, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0923","authenticated-orcid":true,"given":"Ana","family":"Aparicio","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-7127","authenticated-orcid":true,"given":"Di","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA."},{"name":"University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1941.01210140043004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc4016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.05.026"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1259"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11125"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.025"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902651116"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-2948"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001294"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.02.026"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.1584"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70189-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10547"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01600-6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002919"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2584"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2428"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2500"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200839028"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802423105"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni967"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2016.49"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709802104"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1068"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21615-4"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181f1939d"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3097"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2852"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.03.005"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.09.004"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34190"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00323-2"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0715"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-4221"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0821-8"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.01.002"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02284-w"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00613-6"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00795-2"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03918"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09677"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00215-0"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4161"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.69"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.02.003"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1352"},{"key":"e_1_3_3_52_2","doi-asserted-by":"crossref","first-page":"e0130126","DOI":"10.1371\/journal.pone.0130126","article-title":"B7-H3 promotes pathogenesis of autoimmune disease and inflammation by regulating the activity of different T cell subsets","volume":"10","author":"Luo L.","year":"2015","unstructured":"L.\u00a0Luo, G.\u00a0Zhu, H.\u00a0Xu, S.\u00a0Yao, G.\u00a0Zhou, Y.\u00a0Zhu, K.\u00a0Tamada, L.\u00a0Huang, A. D.\u00a0Flies, M.\u00a0Broadwater, W.\u00a0Ruff, J. M.\u00a0van Deursen, I.\u00a0Melero, Z.\u00a0Zhu, L.\u00a0Chen, B7-H3 promotes pathogenesis of autoimmune disease and inflammation by regulating the activity of different T cell subsets. PLOS ONE 10, e0130126 (2015).","journal-title":"PLOS ONE"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21676"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.039"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11950"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.4062"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90071-X"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.459"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4376"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.303"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-125435"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0100"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004424"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.05.012"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04522-6"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04833-8"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03357-x"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00205"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adf6724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:48:57Z","timestamp":1705427337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adf6724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":70,"journal-issue":{"issue":"695","published-print":{"date-parts":[[2023,5,10]]}},"alternative-id":["10.1126\/scitranslmed.adf6724"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adf6724","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"assertion":[{"value":"2022-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadf6724"}}