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Adv."],"published-print":{"date-parts":[[2026,7,24]]},"abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) presents a substantial challenge due to its resistance to cancer treatments. This limited efficacy is, in part, attributed to the immunosuppressive tumor microenvironment (TME), which impairs effector T (T\n                    <jats:sub>eff<\/jats:sub>\n                    ) cell activity. Interleukin-2 (IL-2) is a key cytokine for T cell activation, but its therapeutic use is limited by a short half-life, systemic toxicity, and regulatory T (T\n                    <jats:sub>reg<\/jats:sub>\n                    ) activation. To address this limitation, we engineered\n                    <jats:italic toggle=\"yes\">Bifidobacterium longum<\/jats:italic>\n                    , a probiotic obligate anaerobe that selectively colonizes the TME, to continuously secrete Super-mutant IL-2 (SumIL-2), an engineered IL-2 variant that preferentially activates T\n                    <jats:sub>eff<\/jats:sub>\n                    cells over T\n                    <jats:sub>reg<\/jats:sub>\n                    cells, thereby delivering SumIL-2 selectively to the tumor (BifidoSumIL-2). Systemic administration of BifidoSumIL-2 significantly suppressed tumor growth in both subcutaneous tumors and orthotopic PDAC in mice, inducing an improved T\n                    <jats:sub>eff<\/jats:sub>\n                    \/T\n                    <jats:sub>reg<\/jats:sub>\n                    ratio. Combining BifidoSumIL-2 with chemotherapy, radiation, and immunotherapy further restrained orthotopic PDAC growth, highlighting its therapeutic potential for difficult-to-treat cancers like PDAC.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz1388","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:58:55Z","timestamp":1784829535000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Engineered probiotic\n                    <i>Bifidobacterium<\/i>\n                    for tumor-targeted pancreatic cancer therapy"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0738-8071","authenticated-orcid":true,"given":"Jaehyun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9328-5655","authenticated-orcid":true,"given":"Kaiting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA."},{"name":"The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8110-9021","authenticated-orcid":true,"given":"Christina A.","family":"Nowicki","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA."},{"name":"The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0696-6407","authenticated-orcid":true,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA."},{"name":"The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-6573","authenticated-orcid":true,"given":"Kangdi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA."},{"name":"The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5445-9313","authenticated-orcid":true,"given":"Emile","family":"Naccasha","sequence":"additional","affiliation":[{"name":"Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA."},{"name":"The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7837-8407","authenticated-orcid":true,"given":"Zhichen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern, Dallas, TX 75390, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8441-6617","authenticated-orcid":true,"given":"Yang-Xin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. 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