{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:12:34Z","timestamp":1777896754370,"version":"3.51.4"},"reference-count":117,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am Soc Clin Oncol Educ Book"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>Immune checkpoint inhibitors are cancer therapeutics that have shown remarkable success in extending lives in many cancers, including melanoma, MSI-high cancers, and other cancers. However, these therapeutics have not shown benefit for many patients with cancer, especially those with advanced cancer diagnoses. In addition, many patients develop resistance to these therapeutics and\/or life-altering adverse events that can include cardiotoxicity, pneumonitis, thyroiditis, pancreatitis, and hepatitis. Extensive efforts to improve cancer care by uncovering mechanisms of resistance to immune therapy in solid tumors have led to identification of new sources of resistance and to the development of new approaches to activate or sustain antitumor immunity. Chronic stimulation of T cells by tumors and by checkpoint inhibitors can lead to a progressive state of T-cell exhaustion. Chronic T-cell activation by the tumor microenvironment (TME) or immune therapeutics can upregulate the expression and function of alternate checkpoints, including the T-cell protein LAG-3. Persistent interferon signaling in the TME can drive epigenetic changes in cancer cells that enable tumors to counter immune activation and disrupt tumor cell elimination. In addition, immune-suppressive macrophages can flood tumors in response to signals from dying tumor cells, further preventing effective immune responses. New clinical developments and\/or approvals for therapies that target alternate immune checkpoints, such as the T-cell checkpoint LAG-3; myeloid cell proteins, such as the kinase phosphoinositide 3-kinase gamma isoform; and chronic interferon signaling, such as Jak 1 inhibitors, have been approved for cancer care or shown promise in recent clinical trials.<\/jats:p>","DOI":"10.1200\/edbk-25-481556","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T19:59:17Z","timestamp":1746647957000},"source":"Crossref","is-referenced-by-count":1,"title":["One Step Ahead: Preventing Tumor Adaptation to Immune Therapy"],"prefix":"10.1200","volume":"45","author":[{"given":"Erica L.","family":"Braverman","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA"},{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana P.","family":"Mognol","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy J.","family":"Minn","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario A.A.","family":"Vignali","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA"},{"name":"Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA"},{"name":"Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9251-0600","authenticated-orcid":false,"given":"Judith A.","family":"Varner","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA"},{"name":"Department of Pathology, University of California, San Diego, La Jolla, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5256.1734"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.1089.65.3"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12180"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2407417"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.112"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1129465"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-024-00700-2"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36979-y"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.36401\/JIPO-22-7"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01723-z"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1683"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01523-3"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0522"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4572"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.10.010"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10755"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.013"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf1329"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade8520"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2024.200773"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00574-3"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29050247"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0522-3"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414428"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-021-00574-0"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2024.10.009"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001014"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109970"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.9587"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152351"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02172"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1449"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02593-0"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.9508"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06696-z"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz163"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/1758835919854238"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-020-00314-3"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-1346"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3313"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.6_suppl.436"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009160"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.04.016"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2025.2473165"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","unstructured":"Chen YW Panian J Rose B et al: Recent developments in the management of renal cell cancer. JCO Oncol Pract 10.1200\/OP-24-00875 [epub ahead of print on March 6 2025]","DOI":"10.1200\/OP-24-00875"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0873"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.013"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010612"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.02.003"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1177\/17588359251317144"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1507"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08290-3"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.837645"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01216-z"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5674"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2025.01.008"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00633-1"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19834"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20554"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi6887"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29471-6"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016430108"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.02.009"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade2292"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55770-1"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01687-8"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41470-9"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.171.5.1393"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1620"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01176-4"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","unstructured":"Jiang Y Dai A Huang Y et al: Ligand-induced ubiquitination unleashes LAG3 immune checkpoint function by hindering membrane sequestration of signaling motifs. Cell 10.1016\/j.cell.2025.02.014 [epub ahead of print on March 6 2025]","DOI":"10.1016\/j.cell.2025.02.014"},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00241263"},{"key":"e_1_3_5_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51930-5"},{"key":"e_1_3_5_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.03.013"},{"key":"e_1_3_5_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.010"},{"key":"e_1_3_5_83_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1112672"},{"key":"e_1_3_5_84_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00259-9"},{"key":"e_1_3_5_85_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2310866121"},{"key":"e_1_3_5_86_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300673"},{"key":"e_1_3_5_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.016"},{"key":"e_1_3_5_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.036"},{"key":"e_1_3_5_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"e_1_3_5_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.018"},{"key":"e_1_3_5_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601520"},{"key":"e_1_3_5_92_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abc2728"},{"key":"e_1_3_5_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36942-3"},{"key":"e_1_3_5_94_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02558-7"},{"key":"e_1_3_5_95_2","doi-asserted-by":"publisher","unstructured":"Li H Zandberg DP Kulkarni A et al: Distinct CD8+ T cell dynamics associate with response to neoadjuvant cancer immunotherapies. Cancer Cell 10.1016\/j.ccell.2025.02.026 [epub ahead of print on March 12 2025]","DOI":"10.1016\/j.ccell.2025.02.026"},{"key":"e_1_3_5_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00603-1"},{"key":"e_1_3_5_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1443"},{"key":"e_1_3_5_98_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121015"},{"key":"e_1_3_5_99_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00487"},{"key":"e_1_3_5_100_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02178"},{"key":"e_1_3_5_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.017"},{"key":"e_1_3_5_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.05.005"},{"key":"e_1_3_5_103_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3593"},{"key":"e_1_3_5_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.07.019"},{"key":"e_1_3_5_105_2","first-page":"43","article-title":"Cancer cells resistant to immune checkpoint blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction","volume":"4","author":"Qiu J","year":"2023","unstructured":"Qiu J, Xu B, Ye D, et al: Cancer cells resistant to immune checkpoint blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction. Nat Cancer 4:43-61, 2023","journal-title":"Nat Cancer"},{"key":"e_1_3_5_106_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007445"},{"key":"e_1_3_5_107_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.022"},{"key":"e_1_3_5_108_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.013"},{"key":"e_1_3_5_109_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.020"},{"key":"e_1_3_5_110_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0218-0"},{"key":"e_1_3_5_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.002"},{"key":"e_1_3_5_112_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.02.011"},{"key":"e_1_3_5_113_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-0843-3366"},{"key":"e_1_3_5_114_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23177"},{"key":"e_1_3_5_115_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923"},{"key":"e_1_3_5_116_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0352-8"},{"key":"e_1_3_5_117_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.001"},{"key":"e_1_3_5_118_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.003"}],"container-title":["American Society of Clinical Oncology Educational Book"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/EDBK-25-481556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T19:59:20Z","timestamp":1746647960000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/EDBK-25-481556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":117,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1200\/EDBK-25-481556"],"URL":"https:\/\/doi.org\/10.1200\/edbk-25-481556","relation":{},"ISSN":["1548-8748","1548-8756"],"issn-type":[{"value":"1548-8748","type":"print"},{"value":"1548-8756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"article-number":"e481556"}}