Research Progress on the Mechanism of Anti-Tumor Immune Response Induced by TTFields

Our plain-English summary of Research Progress on the Mechanism of Anti-Tumor Immune Response Induced by TTFields, by Y. Lan, S. Zhang, Y. Pan, et al (Cancers, 2023).

The study

• Authors: Y. Lan, S. Zhang, Y. Pan, M. Wang, G. Chen
• Journal: Cancers
• Published: 2023;15(23)
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tumor treating fields (TTFields), a biophysical therapy technology that uses alternating electric fields to inhibit tumor proliferation, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of newly diagnosed or recurrent glioblastomas (GBM) and malignant pleural mesotheliomas (MPM). Clinical trials have confirmed that TTFields are effective in slowing the tumor growth and prolonging patient survival. In recent years, many researchers have found that TTFields can induce anti-tumor immune responses, and their main mechanisms include upregulating the infiltration ratio and function of immune cells, inducing the immunogenic cell death of tumor cells, modulating immune-related signaling pathways, and upregulating the expression of immune checkpoints. Treatment regimens combining TTFields with tumor immunotherapy are emerging as a promising therapeutic approach in clinical practice. Given the increasing number of recently published studies on this topic, we provide an updated review of the mechanisms and clinical implications of TTFields in inducing anti-tumor immune responses. This review not only has important reference value for an in-depth study of the anticancer mechanism of TTFields but also provides insights into the future clinical application of TTFields.

In plain English

This article was a review, not a new study. The authors summarized published laboratory, animal and clinical research on tumor treating fields (TTFields), a therapy that delivers low-intensity alternating electric fields to a tumor through electrodes placed on the skin. Most of the work they discussed concerned glioblastoma, a brain cancer. Malignant pleural mesothelioma was mentioned briefly. The authors noted that TTFields are FDA-approved for it. They also stated that phase II data showed TTFields plus pemetrexed improved overall survival in these patients, but cited a glioblastoma trial for this. The article did not discuss asbestos. The studies reviewed reported several effects of TTFields: more immune cells entering tumors in animal glioma models, signs of immunogenic cell death in tumor cell lines, changes in immune-related signaling, and higher levels of immune checkpoint proteins such as PD-L1 on tumor cells. In a Lewis lung cancer mouse model, TTFields plus anti-PD1 treatment limited tumor volume significantly more than single treatment. The authors noted that the studies did not confirm immunogenic cell death was necessary for the anti-tumor effect. They concluded that TTFields activate anti-tumor immune responses, but that the exact mechanism remains unclear.

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: narrative review of published preclinical and clinical studies; no search method or study count given
• Who was studied: Published studies of TTFields in tumor cell lines, animal models (mainly glioma or glioblastoma, also Lewis lung cancer) and patients, mainly with glioblastoma; number of studies not stated
• Exposure: Tumor treating fields: low-intensity (1 to 3 V/cm), medium-frequency (100 to 300 kHz) alternating electric fields applied through skin electrodes, alone or combined with chemotherapy or immune checkpoint inhibitors. No asbestos exposure was studied.
• Main results:
  • The authors stated that TTFields are FDA-approved for newly diagnosed or recurrent glioblastoma and for malignant pleural mesothelioma.
  • The authors stated, without numbers, that phase II data showed TTFields plus pemetrexed improved overall survival in malignant pleural mesothelioma patients. The reference they cite for this (reference 12) is a glioblastoma trial of TTFields plus temozolomide.
  • The review cited a survey of glioblastoma patients treated with TTFields. Those receiving more than 4.1 milligrams of dexamethasone daily (n = 64) had a median survival of 4.8 months. Those receiving 4.1 milligrams or less daily (n = 56) had a median survival of 11 months (p less than 0.0001).
  • Cited studies found markers of immunogenic cell death in TTFields-treated tumor cell lines. The authors noted these studies did not confirm that immunogenic cell death was necessary for the anti-tumor effect.
  • A cited single-cell sequencing study reported that immune checkpoints (PD-L1, CTLA-4, TIGIT) were upregulated on tumor cells after TTFields.
  • In a cited Lewis lung cancer mouse model, TTFields combined with anti-PD1 limited tumor volume significantly more than single treatment.
• The authors' conclusion: The authors concluded that in vivo, in vitro and clinical results confirm that TTFields activate and enhance anti-tumor immune responses. They added that, without clear molecular mechanisms, choosing an optimal combination therapy remains challenging.
• Limitations the authors state:
  • The research reviewed mostly observed immune-cell changes before and after TTFields. Little work examined whether TTFields caused those changes.
  • The specific mechanism by which TTFields enhance anti-tumor immune responses is still unclear.
  • Evidence on whether reduced metastasis in an animal model was directly related to immune activation is lacking.

Topics

Medical terms in this study, explained in our Lexicon: Tumor Treating Fields (TTFields), Pleural Mesothelioma, Clinical Trial, Immunotherapy.

Related studies

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• Persistent mutation burden drives sustained anti-tumor immune responses — N. Niknafs, A. Balan, et al. (2023)
• The schemes, mechanisms and molecular pathway changes of Tumor Treating Fields (TTFields) alone or in combination with radiotherapy and chemotherapy — G. Tanzhu, L. Chen, et al. (2022)
• The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields) — K. Wainer-Katsir, A. Haber, et al. (2025)
• Deep dive into the immune response against murine mesothelioma permits design of novel anti-mesothelioma therapeutics — E. Stern, S. Caruso, et al. (2022)
• Dysautonomia and dysosmia associated with anti-Hu antibodies induced by immune checkpoint inhibitors: a case report — M. Fujimoto, K. Igari, et al. (2026)

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