{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T09:44:14Z","timestamp":1774604654501,"version":"3.50.1"},"reference-count":73,"publisher":"American Association for Cancer Research (AACR)","issue":"8","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery\/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacologic inhibition of angiotensin-II type-1 receptor reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSC) in obesity is induced by tumor-associated neutrophils (TAN) recruited by adipocyte-secreted IL1\u03b2. PSCs further secrete IL1\u03b2, and inactivation of PSCs reduces IL1\u03b2 expression and TAN recruitment. Furthermore, depletion of TANs, IL1\u03b2 inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In patients with pancreatic cancer, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that cross-talk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity.<\/jats:p>\n                  <jats:p>Significance: Considering the current obesity pandemic, unraveling the mechanisms underlying obesity-induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity-promoted PDAC progression. Importantly, we discovered that clinically available antifibrotic\/inflammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852\u201369. \u00a92016 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Bronte and Tortora, p. 821.<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 803<\/jats:p>","DOI":"10.1158\/2159-8290.cd-15-1177","type":"journal-article","created":{"date-parts":[[2016,5,31]],"date-time":"2016-05-31T22:48:30Z","timestamp":1464734910000},"page":"852-869","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":380,"title":["Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy"],"prefix":"10.1158","volume":"6","author":[{"given":"Joao","family":"Incio","sequence":"first","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"2Department of Internal Medicine, Hospital S. Joao, Porto, Portugal."},{"name":"3I3S, Institute for Innovation and Research in Heath, Metabolism, Nutrition and Endocrinology Group, Biochemistry Department, Faculty of Medicine, Porto University, Porto, Portugal."}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"4Biology and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Priya","family":"Suboj","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"5Department of Botany and Biotechnology, St. Xaviers College, Thumba, Trivandrum, Kerala, India."}]},{"given":"Shan M.","family":"Chin","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Ivy X.","family":"Chen","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"6Harvard School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts."}]},{"given":"Matthias","family":"Pinter","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Mei R.","family":"Ng","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Hadi T.","family":"Nia","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Jelena","family":"Grahovac","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Shannon","family":"Kao","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Suboj","family":"Babykutty","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"7Department of Zoology, Mar Ivanios College, Nalanchira, Trivandrum, Kerala, India."}]},{"given":"Yuhui","family":"Huang","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Keehoon","family":"Jung","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Nuh N.","family":"Rahbari","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Xiaoxing","family":"Han","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Vikash P.","family":"Chauhan","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"John D.","family":"Martin","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Julia","family":"Kahn","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Peigen","family":"Huang","sequence":"additional","affiliation":[{"name":"1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Vikram","family":"Desphande","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"James","family":"Michaelson","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"9Laboratory for Quantitative Medicine, and Division of Surgical Oncology, Gillette Center for Women\u2019s Cancers, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts."}]},{"given":"Theodoros P.","family":"Michelakos","sequence":"additional","affiliation":[{"name":"10Departments of Gastroenterology and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Cristina R.","family":"Ferrone","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."},{"name":"10Departments of Gastroenterology and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts."}]},{"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"3I3S, Institute for Innovation and Research in Heath, Metabolism, Nutrition and Endocrinology Group, Biochemistry Department, Faculty of Medicine, Porto University, Porto, Portugal."}]},{"given":"Yves","family":"Boucher","sequence":"additional","affiliation":[{"name":"1Edwin L. 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