Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel

Our plain-English summary of Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel, by T. Kan, T. Haj Khalil, Y. Barsheshet, et al (International Journal of Cancer, 2026).

The study

• Authors: T. Kan, T. Haj Khalil, Y. Barsheshet, T. Voloshin, L. Koren, B. Koltun, C. David, K. Wainer-Katsir, A. Vorontsova, B. Brant, S. Zisman-Rozen, H.M. Ene, R. Frechtel-Gerzi, S. Cahal, A. Klein-Goldberg, L. Lifshitz, E. Zemer Tov, M. Shai, A. Haber, M. Giladi, U. Weinberg, Y. Palti
• Journal: International Journal of Cancer
• Published: 2026;158(12):3091-3100
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tumor Treating Fields (TTFields) are an approved cancer therapy for glioblastoma (GBM), pleural mesothelioma, and non-small cell lung cancer (NSCLC). A recent phase 3 trial of TTFields therapy concomitant with standard-of-care gemcitabine and nab-paclitaxel (Gem/NabP) as a first-line 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-Myc. In the current study, TTFields application significantly suppressed c-Myc expression and induced immunogenic cell death (ICD)-characterized by increased calreticulin cell-surface exposure, extracellular ATP secretion, and elevated HMGB1 release-in pancreatic cancer models. These effects were further enhanced when TTFields were applied concomitantly with Gem/NabP. Causality between c-Myc 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-derived suppressor cells (M-MDSC), and increased the tumor lymphocyte-to-monocyte ratio (LMR) compared to all other treatment groups. These findings support the potential of TTFields to enhance therapeutic efficacy. Moreover, TTFields-induced 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.

© 2026 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

In plain English

This short report is not about asbestos. It was a laboratory and animal study of Tumor Treating Fields (TTFields), a treatment that uses low-intensity electric fields. The authors tested it in pancreatic ductal adenocarcinoma, a type of pancreatic cancer, alone and together with the chemotherapy drugs gemcitabine and nab-paclitaxel. They used two human and one mouse pancreatic cancer cell line, and mice with tumors grown in the pancreas. In the cells, TTFields lowered c-Myc, a gene that controls cell growth. Combined with chemotherapy, TTFields reduced cell counts and raised markers of a kind of cell death that can alert the immune system more than either treatment alone. The combination did not lower c-Myc protein more than TTFields alone, and the authors did not claim a link between c-Myc and the immune findings. In mice, the combination improved tumor control more than either treatment alone. Tumors in this group had a lower share of monocytic myeloid-derived suppressor cells, a type of immune-suppressing cell, among their immune cells, and a higher lymphocyte-to-monocyte ratio. The authors concluded that the findings support further study of TTFields with chemotherapy and immunotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: preclinical laboratory study (short report): experiments on cancer cell lines plus an experiment in mice with tumors implanted in the pancreas
• Who was studied: Human pancreatic ductal adenocarcinoma cell lines AsPC-1 and BxPC-3 and the mouse cell line Panc02. Also male C57Bl/6 mice, 10 weeks old, injected in the pancreas with Panc02 cells and randomized into four groups. The number of mice is not stated.
• Exposure: No asbestos exposure was studied. The exposures were TTFields at 150 kHz (1.7 V/cm RMS for 24, 48 or 72 h in cells; 4.4 to 5.6 V/cm RMS continuously for 10 days in mice) or sham (heat), with or without gemcitabine/nab-paclitaxel. In mice the drugs were given at 50 mg/kg each by injection into the abdomen on days 14 and 21.
• Main results:
  • In AsPC-1 and BxPC-3 cells, TTFields lowered c-Myc RNA levels, a statistically significant reduction in both cell lines after 72 h.
  • In the cell lines, chemotherapy or TTFields alone reduced cell count and the share of viable cells. These effects were significantly enhanced when the two were given together.
  • Each treatment alone raised markers of immunogenic cell death (HMGB1 release, eIF2α phosphorylation, calreticulin exposure, ATP secretion). Giving both together significantly enhanced these effects.
  • TTFields alone lowered c-Myc protein more than chemotherapy did. The combination did not lower c-Myc further than TTFields alone.
  • In the mice, each treatment alone showed antitumor activity, and the combination significantly enhanced tumor control compared with either alone.
  • In mouse blood, TTFields alone increased effector memory CD8+ T cells. This increase was smaller when TTFields were combined with chemotherapy.
  • In mouse tumors, total leukocytes increased with TTFields and with the combination; the increase with the combination was not statistically significant.
  • In the combination group, tumors showed a lower proportion of monocytic myeloid-derived suppressor cells among tumor CD45+ leukocytes and a higher tumor lymphocyte-to-monocyte ratio.
• The authors' conclusion: The authors concluded that TTFields may enhance standard chemotherapy for pancreatic ductal adenocarcinoma. They said the findings give a rationale for future study of TTFields with chemotherapy and immunotherapy.
• Limitations the authors state:
  • The authors did not establish a mechanistic link between the c-Myc changes and the immune findings.
  • The authors said their view of c-Myc as one of several contributing effects needs direct testing.

Topics

Medical terms in this study, explained in our Lexicon: Tumor Treating Fields (TTFields), Adenocarcinoma, Gemcitabine, Pleural Mesothelioma, Non-Small Cell Lung Cancer, Unresectable, Overall Survival, High Mobility Group Box 1 (HMGB1).

Related studies

• Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models — H. Mumblat, A. Martinez-Conde, et al. (2021)
• Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook — G.L. Ceresoli, L. Gianoncelli (2025)
• Management of Peritoneal Metastasis in Patients with Pancreatic Ductal Adenocarcinoma — G. Wu, O.J. Standring, et al. (2025)
• Expression of Calretinin, Marker of Mesothelial Differentiation, in Pancreatic Ductal Adenocarcinoma: A Potential Diagnostic Pitfall — G. Askan, O. Basturk (2021)
• Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model — L. Kuryk, E. Haavisto, et al. (2016)
• Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix — T. Kulkarni, S. Banik, et al. (2025)

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