IMST-30. EVALUATING THE IN-VITRO EFFECTS OF TUMOR-TREATING FIELDS ON T-CELL RESPONSES

Abstract

Tumor Treating Fields (TTFields) are low-intensity electrical fields that target proliferating cells by hindering the formation of mitotic spindle and the translocation of charged organelles. Combining TTFields with immune-based therapies is a rational approach as they possess different mechanisms of action (MOA). Conversely, TTFields may potentially abrogate various cellular functions required for effective T cell responses. In this study we evaluated the effect of TTFields on select human T cell functions which are pivotal for an effective anti-tumoral response. Peripheral blood mononuclear cells (PBMC) were isolated from healthy donors. Cells were cultured with or without Phytohemaglutenin (PHA, an activating mitogenic superantigen) and under normal versus TTFields conditions. Cellular responses were monitored using an 8-color flow cytometry panel concurrently evaluating proliferation (CFSE), cytokine secretion (IFNɣ), cytotoxic degranulation (CD107a), and T cell activation/exhaustion (PD1 expression). TTFields did not alter the functionality of non-activated T cells. Viable, PHA-activated T cells treated with TTFields exhibited no change in their PD1 up-regulation (activation), in their IFNγ secretion and in their CD107a surface-expression (cytotoxicity). Viable, PHA-activated T cells exhibited reduced proliferation, in line with TTFields known MOA. Polyfunctionality, e.g., the secretion of more than one cytokine by a single T cell, is associated with effective anti-pathogen and anti-tumoral responses. A polyfunctionality analysis of the activated T cells demonstrated that under TTFields conditions, T cells that had lost the capacity to proliferate retained all other polyfunctional /combinatorical immune functions. All findings were true both for T helpers and for cytotoxic T cells. Pivotal T cell response parameters, with the exception of proliferation, were found to be unhindered by TTFields. The data suggests that the integration of TTFields with various immunotherapeutic approaches may be a rational approach to explore for the treatment of brain tumors.