{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:03:54Z","timestamp":1789473834799,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010253","name":"Secretar\u00eda de Ciencia y T\u00e9cnica, Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020220400220BA"],"award-info":[{"award-number":["20020220400220BA"]}],"id":[{"id":"10.13039\/501100010253","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by poor prognosis and limited response to gemcitabine, the standard first\u2010line chemotherapy. One major contributor to chemoresistance is autophagy, a process frequently upregulated in PDAC. In this study, we examined the ability of type I interferons (IFN\u03b12b and IFN\u03b21a) to modulate autophagy and disturb tumor cell resistance to gemcitabine. PDAC cells were treated with increasing concentrations of IFN\u03b12b or IFN\u03b21a, and cell proliferation was assessed by [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010thymidine incorporation. Apoptosis was evaluated by TUNEL staining following treatments with interferons and\/or gemcitabine. STAT1 phosphorylation was analyzed as a marker of downstream type I interferon signaling. Autophagy was analyzed by western blot for LC3B, Beclin\u20101, Bcl\u2010XL and p62\/SQSTM1, and by quantifying autophagic flux using mCherry\u2010EGFP\u2010LC3B\u2010transfected cells in the presence or absence of lysosomal inhibitors. We found that IFN\u03b12b promoted autophagic flux and reduced gemcitabine\u2010induced cell death, indicating a cytoprotective role. In contrast, IFN\u03b21a reduced autophagosome formation and significantly enhanced cell death, without clear evidence of altering autophagic flux. Both interferons induced STAT1 phosphorylation, confirming engagement of downstream type I interferon signaling. Our findings highlight the contrasting roles of IFN\u03b12b and IFN\u03b21a in the regulation of autophagy and gemcitabine response and suggest that IFN\u03b21a, by reducing autophagosome formation, may sensitize PDAC cells to chemotherapy. These findings identify IFN\u03b21a as a potential chemosensitizing agent in PDAC and provide a rationale for further evaluating combinations of IFN\u03b21a, gemcitabine, and autophagy\u2010targeting strategies to overcome chemoresistance.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70342","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:16:18Z","timestamp":1789470978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type I interferons modulate autophagy to shape gemcitabine response in pancreatic cancer cells"],"prefix":"10.1002","author":[{"given":"Lucy E.","family":"Bonilla","sequence":"first","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn M.","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Unidad de Conocimiento Traslacional, Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda  Buenos Aires Argentina"},{"name":"Centro de Investigaciones en Biomedicina traslacional CIBiMeT, CONICET \u2010 Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago A.","family":"Behr","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas A.","family":"Pibuel","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda L.","family":"Palanek","sequence":"additional","affiliation":[{"name":"Unidad de Conocimiento Traslacional, Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda  Buenos Aires Argentina"},{"name":"Centro de Investigaciones en Biomedicina traslacional CIBiMeT, CONICET \u2010 Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Grasso","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"},{"name":"C\u00e1tedra de Fisiopatolog\u00eda, Departamento de Ciencias Biol\u00f3gicas, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria N.","family":"Garcia","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Garona","sequence":"additional","affiliation":[{"name":"Centro de Medicina Traslacional (CEMET) Unidad de Investigaciones Biom\u00e9dicas en C\u00e1ncer (IBioCAN, Unidad N\u00b06), Hospital de Alta Complejidad en Red El Cruce \u201cDr. N\u00e9stor Carlos Kirchner\u201d S.A.M.I.C. Florencio Varela, Buenos Aires, Argentina."},{"name":"Centro de Oncolog\u00eda Molecular y Traslacional (COMTra) Unidad de Oncolog\u00eda Traslacional, Universidad Nacional de Quilmes. Quilmes, Buenos Aires, Argentina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina L.","family":"Lompard\u00eda","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elida","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Inmunolog\u00eda, Departamento de Microbiolog\u00eda, Inmunolog\u00eda, Biotecnolog\u00eda y Gen\u00e9tica, Facultad de Farmacia y Bioqu\u00edmica Universidad de Buenos Aires  Argentina"},{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), UBA \u2013 CONICET  Buenos Aires 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