{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:09:50Z","timestamp":1791544190244,"version":"4.3.4"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"26","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:p>\n            Immune checkpoint inhibitor (ICI) therapy is effective against many cancers for a subset of patients; a large percentage of patients remain unresponsive to this therapy. One contributing factor to ICI resistance is accumulation of monocytic myeloid-derived suppressor cells (M-MDSCs), a subset of innate immune cells with potent immunosuppressive activity against T lymphocytes. Here, using lung, melanoma, and breast cancer mouse models, we show that CD73-expressing M-MDSCs in the tumor microenvironment (TME) exhibit superior T cell suppressor function. Tumor-derived PGE\n            <jats:sub>2<\/jats:sub>\n            , a prostaglandin, directly induces CD73 expression in M-MDSCs via both Stat3 and CREB. The resulting CD73 overexpression induces elevated levels of adenosine, a nucleoside with T cell\u2013suppressive activity, culminating in suppression of antitumor CD8\n            <jats:sup>+<\/jats:sup>\n            T cell activity. Depletion of adenosine in the TME by the repurposed drug PEGylated adenosine deaminase (PEG-ADA) increases CD8\n            <jats:sup>+<\/jats:sup>\n            T cell activity and enhances response to ICI therapy. Use of PEG-ADA can therefore be a therapeutic option to overcome resistance to ICIs in cancer patients.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adg3736","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T17:58:21Z","timestamp":1688147901000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":84,"title":["Monocytic MDSCs exhibit superior immune suppression via adenosine and depletion of adenosine improves efficacy of immunotherapy"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-9088","authenticated-orcid":true,"given":"Omar S.","family":"Sarkar","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-1660","authenticated-orcid":true,"given":"Howard","family":"Donninger","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY, USA."},{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA."},{"name":"Experimental Therapeutics Program, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Numan","family":"Al Rayyan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY, USA."},{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA."},{"name":"Natural Agricultural Research Center, P.O. Box 639, Baq'a 19381, Jordan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis C.","family":"Chew","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce","family":"Stamp","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-6313","authenticated-orcid":true,"given":"Xiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-2652","authenticated-orcid":true,"given":"Aaron","family":"Whitt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and 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A.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA."},{"name":"Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, KY, USA."},{"name":"Immuno-Oncology Group, Brown Cancer Center, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1933-8178","authenticated-orcid":true,"given":"Alfred","family":"Zippelius","sequence":"additional","affiliation":[{"name":"Center for Immunotherapy, Cancer Center Medical Oncology, University Hospital Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Eaton","sequence":"additional","affiliation":[{"name":"James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA."},{"name":"Immuno-Oncology Group, Brown Cancer Center, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-8278","authenticated-orcid":true,"given":"Jason A.","family":"Chesney","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY, USA."},{"name":"Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, KY, USA."},{"name":"Immuno-Oncology Group, Brown Cancer Center, University of Louisville, Louisville, KY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-4587","authenticated-orcid":true,"given":"Kavitha","family":"Yaddanapudi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA."},{"name":"Department of Surgery, Division of Immunotherapy, University of Louisville, Louisville, KY, USA."},{"name":"Immuno-Oncology Group, Brown Cancer Center, University of 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