T cells retain pivotal antitumoral functions under tumor-treating electric fields

Gil Diamant, Hadar Simchony Goldman, Lital Gasri Plotnitsky, Marina Roitman, Tamar Shiloach, Anat Globerson-Levin, Zelig Eshhar, Oz Haim, Niv Pencovich, Rachel Grossman, Zvi Ram, Ilan Volovitz

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor-treating fields (TTFields) are a localized, antitumoral therapy using alternating electric fields, which impair cell proliferation. Combining TTFields with tumor immunotherapy constitutes a rational approach; however, it is currently unknown whether TTFields' locoregional effects are compatible with T cell functionality. Healthy donor PBMCs and viably dissociated human glioblastoma samples were cultured under either standard or TTFields conditions. Select pivotal T cell functions were measured by multiparametric flow cytometry. Cytotoxicity was evaluated using a chimeric Ag receptor (CAR)-T-based assay. Glioblastoma patient samples were acquired before and after standard chemoradiation or standard chemoradiation + TTFields treatment and examined by immunohistochemistry and by RNA sequencing. TTFields reduced the viability of proliferating T cells, but had little or no effect on the viability of nonproliferating T cells. The functionality of T cells cultured under TTFields was retained: they exhibited similar IFN-g secretion, cytotoxic degranulation, and PD1 upregulation as controls with similar polyfunctional patterns. Glioblastoma Ag-specific T cells exhibited unaltered viability and functionality under TTFields. CAR-T cells cultured under TTFields exhibited similar cytotoxicity as controls toward their CAR target. Transcriptomic analysis of patients' glioblastoma samples revealed a significant shift in the TTFields-treated versus the standard-treated samples, from a protumoral to an antitumoral immune signature. Immunohistochemistry of samples before and after TTFields treatment showed no reduction in T cell infiltration. T cells were found to retain key antitumoral functions under TTFields settings. Our data provide a mechanistic insight and a rationale for ongoing and future clinical trials that combine TTFields with immunotherapy.

Original languageEnglish
Pages (from-to)709-719
Number of pages11
JournalJournal of Immunology
Volume207
Issue number2
DOIs
StatePublished - 15 Jul 2021

Fingerprint

Dive into the research topics of 'T cells retain pivotal antitumoral functions under tumor-treating electric fields'. Together they form a unique fingerprint.

Cite this