{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T11:48:26Z","timestamp":1780746506641,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022811","name":"Fondazione Nadia Valsecchi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The pancreatic tumour microenvironment (TME) is a complex ecosystem where tumour cells, cancer\u2010associated fibroblasts and immune cells interact, often in ways that contribute to tumour growth. The role of interleukin (IL17)A in pancreatic cancer progression is now more defined, and it is known to sustain a pro\u2010tumoural microenvironment and inhibit the immune response. Here, we explore the effect of combining IL17A depletion with a cancer vaccine to enhance anti\u2010tumour immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used genetically engineered mice proficient or deficient in IL17A, and orthotopically injected mice with pancreatic tumour cells depleted or not in IL17A, to examine the vaccine effects on tumour growth and immune responses. Both humoral and cellular immune responses were analysed following vaccination in IL17A\u2010deficient and control mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mice lacking IL17A\u2014either genetically or through pharmacological depletion\u2014exhibited prolonged survival and smaller tumours, compared to vaccinated controls. Vaccination in IL17A\u2010deficient mice significantly increased the influx of immune cells, including Natural Killer (NK) and effector\/memory CD8 T cells, which displayed higher cytotoxic activity. CD8 T\u2010cell depletion in these models notably reduced vaccine efficacy, underscoring the essential role of these cells. NK cell depletion in untreated models further demonstrated NK cells\u2019 critical function in controlling tumour growth when IL17A was absent. Overall, IL17A depletion enhanced both antigen\u2010specific humoral and cellular immune responses, indicating a shift towards a more robust and responsive immune environment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal that the absence of IL17A in the pancreatic TME reprograms it into a more immune\u2010supportive environment, favouring the recruitment of effector\/memory immune cells upon vaccination. This approach paves the way for novel therapeutic combinations in pancreatic cancer, where IL17A depletion may boost both immunotherapy efficacy and anti\u2010tumour responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70442","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:33:04Z","timestamp":1755667984000},"source":"Crossref","is-referenced-by-count":2,"title":["The absence of IL17A favours cytotoxic cell function and improves antigen\u2010specific immunotherapies in pancreatic adenocarcinoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Giorgia","family":"Tiberi","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Scagliotti","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermes","family":"Candiello","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Ariadna Diez","family":"Villegas","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Brugiapaglia","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino 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Emato\u2010Oncologia University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro Giulio","family":"Papotti","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences University of Torino, AOU Citt\u00e0 Della Salute E Della Scienza Di Torino  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Adriani","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove  Immunos Singapore Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Novelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences University of Torino  Torino Italy"},{"name":"Molecular Biotechnology Centre \u201cGuido Tarone,\u201d University of Torino  Turin 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