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A recent phase 3 trial of TTFields therapy concomitant with standard\u2010of\u2010care gemcitabine and nab\u2010paclitaxel (Gem\/NabP) as a first\u2010line treatment for unresectable, locally advanced pancreatic adenocarcinoma demonstrated a significant increase in overall survival. The current study evaluated the effects of TTFields in preclinical pancreatic ductal adenocarcinoma (PDAC) models. The vast majority of PDAC patients harbor KRAS mutations, which are associated with a more aggressive disease phenotype and increased therapy resistance, driven in part by overexpression of the key transcription factor c\u2010Myc. In the current study, TTFields application significantly suppressed c\u2010Myc expression and induced immunogenic cell death (ICD)\u2014characterized by increased calreticulin cell\u2010surface exposure, extracellular ATP secretion, and elevated HMGB1 release\u2014in pancreatic cancer models. These effects were further enhanced when TTFields were applied concomitantly with Gem\/NabP. Causality between c\u2010Myc modulation and immune readouts was not established. In vivo, TTFields application induced a systemic immune response, evidenced by dendritic cell activation, increased effector memory T cells, and greater tumor leukocyte infiltration. TTFields concomitant with Gem\/NabP significantly reduced tumor volume, decreased tumor monocytic myeloid\u2010derived suppressor cells (M\u2010MDSC), and increased the tumor lymphocyte\u2010to\u2010monocyte ratio (LMR) compared to all other treatment groups. These findings support the potential of TTFields to enhance therapeutic efficacy. Moreover, TTFields\u2010induced tumor immunogenicity may enable combination strategies with immunotherapies. A phase 2 clinical trial investigating TTFields with Gem\/NabP and immune checkpoint inhibitors (ICIs) for metastatic PDAC is currently underway.<\/jats:p>","DOI":"10.1002\/ijc.70408","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:59:12Z","timestamp":1772989152000},"page":"3091-3100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and immunogenic effects of Tumor Treating Fields (\n                    <scp>TTFields<\/scp>\n                    ) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine\/nab\u2010paclitaxel"],"prefix":"10.1002","volume":"158","author":[{"given":"Tal","family":"Kan","sequence":"first","affiliation":[{"name":"Novocure Ltd.  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharwat","family":"Haj Khalil","sequence":"additional","affiliation":[{"name":"Novocure Ltd.  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