{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:50:59Z","timestamp":1791571859812,"version":"4.3.4"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"41","funder":[{"name":"DOD","award":["HT9425-23-1-0560, PA220024P1"],"award-info":[{"award-number":["HT9425-23-1-0560, PA220024P1"]}]},{"name":"national institute of health","award":["R01CA265410, R01CA212119"],"award-info":[{"award-number":["R01CA265410, R01CA212119"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>\n                    Cytotoxic T cells [cytotoxic lymphocytes (CTLs)] are crucial for adaptive immunity leading to prolonged survival and potential cures for cancer. Recent clinical data have shown that pharmacological inhibition modifies the tumor microenvironment (TME) and activates CTLs, although the mechanism is not well described. In this study, we found that T cell\u2013specific knockout (KO) of the most prevalent SUMO paralog,\n                    <jats:italic toggle=\"yes\">Sumo2<\/jats:italic>\n                    \/\n                    <jats:italic toggle=\"yes\">SUMO2<\/jats:italic>\n                    , in both mouse and human CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells significantly enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation without enhanced IFN-I (type I interferon)\u2013responsive genes in vitro but increased chromatin accessibility at enhancer regions for AP-1 (activating protein 1) family members, including BATF and JunB, which are known to promote T cell activation and proliferation. Using antigen-specific OT1 and CAR (chimeric antigen receptor) T cell models, we found that\n                    <jats:italic toggle=\"yes\">Sumo2<\/jats:italic>\n                    KO CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells had significantly higher tumor infiltration, as revealed by flow cytometry, immunofluorescence staining, and single-nucleus RNA sequencing (snRNA-seq), and conferred greater tumor growth inhibition than wild-type control T cells. snRNA-seq also revealed that\n                    <jats:italic toggle=\"yes\">Sumo2<\/jats:italic>\n                    KO in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells increased the expression of TRAIL (tumor necrosis factor\u2013related apoptosis-inducing ligand) in vivo and activated the antitumor immune microenvironment, likely through cell-cell interaction involving more activated CTLs. These findings elucidate a novel mechanism by which SUMOylation controls CTL activation and tumor infiltration that activate antitumor immunity in the TME. SUMO2 KO can also be a potential strategy to enhance adoptive T cell therapies for solid tumors by enhancing their activation, tumor infiltration and ability to modulate the TME.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef2217","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:06:59Z","timestamp":1791569219000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["SUMO2 deletion changes chromatin accessibility and enhances cytotoxic T cell activation and tumor infiltration"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-121X","authenticated-orcid":true,"given":"Mohottige D.","family":"Neranjan Tharuka","sequence":"first","affiliation":[{"name":"School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-6895","authenticated-orcid":true,"given":"Dai-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa Jurgensen","family":"Amaral","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5241-4022","authenticated-orcid":true,"given":"Tianchen","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3802-0418","authenticated-orcid":true,"given":"Yixuan","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-564X","authenticated-orcid":true,"given":"Shih-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3456-8144","authenticated-orcid":true,"given":"Nikhil","family":"Chilakapati","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-1127","authenticated-orcid":true,"given":"Bing","family":"Ren","sequence":"additional","affiliation":[{"name":"New York Genome Institute, New York, NY 10013, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-7340","authenticated-orcid":true,"given":"Stephen P.","family":"Schoenberger","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Immunology, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5012-4309","authenticated-orcid":true,"given":"Ye","family":"Zheng","sequence":"additional","affiliation":[{"name":"Salk Institute for Biological Sciences, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-182X","authenticated-orcid":true,"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California, San Diego, La Jolla, CA 92037, 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