Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy.

Cancer Immunology, Immunotherapy : CII
Tali VoloshinYoram Palti

Abstract

Tumor-treating fields (TTFields) are alternating electric fields in a specific frequency range (100-300 kHz) delivered to the human body through transducer arrays. In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, damage-associated molecular patterns including high-mobility group B1 and adenosine triphosphate are released and calreticulin is exposed on the cell surface. Moreover, we show that TTFields treatment promotes the engulfment of cancer cells by dendritic cells (DCs) and DCs maturation in vitro, as well as recruitment of immune cells in vivo. Additionally, our study demonstrates that the combination of TTFields with anti-PD-1 therapy results in a significant decline of tumor volume and increase in the percentage of tumor-infiltrating leukocytes in two tumor models. In orthotopic lung tumors, these infiltrating leukocytes, specifically macrophages and DCs, showed elevated expression of PD-L1. Compatibly, cytotoxic T-cells isolated from these tumors demonstrated increased production of IFN-γ. In colon cancer tumors, T-cells infiltration was significantly incre...Continue Reading

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Citations

Nov 5, 2020·British Journal of Cancer·Ola RominiyiSpencer James Collis
May 25, 2021·Frontiers in Oncology·Na Tosha N GatsonMartin Glas
Jul 3, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shiyu LiuXin Jiang
Jul 20, 2021·Neuro-oncology Practice·Ohad RegevTehila Kaisman-Elbaz
Jul 23, 2021·Advanced Science·Elise P W JenkinsGeorge G Malliaras
Jul 4, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gil DiamantIlan Volovitz
Sep 4, 2021·Bioelectricity·Jade A PhillipsMustafa B A Djamgoz
Sep 21, 2021·Drug Delivery and Translational Research·Ahmad Reza FarmaniNima Rezaei

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Methods Mentioned

BETA
Assay
ELISA
flow cytometry
Flow

Clinical Trials Mentioned

NCT02973789

Software Mentioned

FlowJo
Graphpad Prism
Image Studio Lite
TTFields

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