Description:
<jats:title>Abstract</jats:title>
<jats:p>BACKGROUND: 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. TTFields have been approved for treatment of high grade glioma brain malignancies (Glioblastoma, GBM), both recurrent and newly diagnosed. Concurrently, immunotherapeutic approaches for treatment of GBM are considered promising, and multiple strategies are currently being examined in both basic research clinical trials. Combining TTFields with immune-based therapies is a rational approach as they possess markedly different mechanisms of action (MOA). Conversely, TTFields may potentially abrogate various cellular functions required for effective T cell responses. AIM: In this study we perform an in-vitro evaluation of the effect of TTFields on select human T cell functions which are pivotal for an effective anti-tumoral response. Our goal is to ascertain the potential compatibility between immune-based and TTFields therapies. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from healthy donors. Cells were cultured under normal versus TTFields conditions using an In-Vitro TTFields culturing system, either with or without Phytohemaglutenin (PHA, an activating mitogenic superantigen). Cellular responses were monitored using an 8-color flow cytometry panel that concurrently evaluated proliferation (CFSE dilution), cytokine secretion (IFNγ), cytotoxic degranulation (CD107a surface presentation) and T cell activation/ exhaustion (PD1 expression). RESULTS: TTFields did not alter the functionality of non-activated T cells. Viable, PHA-activated T cells cultured under TTFields exhibited no change in PD1 up-regulation, IFNγ secretion and CD107a surface-expression. On the other hand, these T cells exhibited reduced proliferation, which is in line with the known MOA of TTFields. The presence of polyfunctional T cells, e.g. cells that secret more than one type of cytokine, is associated with effective anti-pathogen and anti-tumoral responses. A single-cell level polyfunctionality analysis of the activated T cells demonstrated that even cells that had lost the capacity to proliferate under TTFields conditions still retained all other polyfunctional combinations of immune functions. All findings were true both for T helpers and for cytotoxic T cells. CONCLUSIONS: Pivotal T cell response parameters, with the exception of proliferation, were found to be unhindered by TTFields. Our data suggests that the integration of TTFields with various immunotherapeutic approaches may be a rational strategy to explore for the treatment of brain tumors.</jats:p>
<jats:p>Citation Format: Gil Diamant, Ilan Volovitz, Zvi Ram. Evaluating the in vitro effects of tumor-treating fields on T-cell responses [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B117.</jats:p>