IMMU-71. EVALUATING THE COMPATIBILITY OF TUMOR TREATING ELECTRIC FIELDS WITH KEY ANTI-TUMORAL T CELL FUNCTIONS
Abstract BACKGROUND Combining Tumor Treating electrical Fields (TTFields) with immunotherapy is a rational approach due to their different mechanisms of action (MOA) and to TTFields’ ability to induce immunogenic cell death (ICD). Conversely, TTFields may interfere with immune functions critical for...
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Published in | Neuro-oncology (Charlottesville, Va.) Vol. 20; no. suppl_6; pp. vi137 - vi138 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
US
Oxford University Press
05.11.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
BACKGROUND
Combining Tumor Treating electrical Fields (TTFields) with immunotherapy is a rational approach due to their different mechanisms of action (MOA) and to TTFields’ ability to induce immunogenic cell death (ICD). Conversely, TTFields may interfere with immune functions critical for effective T cell responses.
METHODS
T cells from healthy donors’ peripheral blood or from viably dissociated glioblastoma samples were cultured under normal or TTFields conditions, with or without superantigen-stimulation. Eight-color flow cytometry was used to assess T cell responses by monitoring select pivotal antitumoral functions: proliferation (CFSE), IFNγ secretion, cytotoxic degranulation (CD107a), activation/exhaustion (PD1) and viability. Direct cytotoxicity was evaluated using chimeric antigen receptor (CAR) T cells.
RESULTS
The viability of stimulated T cells that attempted to proliferate decreased under TTFields, in line with TTFields’ MOA. Small or no reductions in viability were found in activated T cells that did not attempt to proliferate and in unstimulated T cells. The functionality of stimulated peripheral-blood T cells and tumor-infiltrating T cells (TILs) under TTFields was unhindered: T cells exhibited comparable PD1 upregulation, IFNγ secretion and CD107a expression as controls. T cell polyfunctionality, associated with effective antitumoral responses, was retained under TTFields conditions. PD1-expressing TILs, a subset containing most of the tumor antigen-specific TILs, exhibited unaltered viability and functionality under TTFields. CAR T-cells, which utilize the same killing machinery as unmodified T cells, exhibited unaltered cytotoxic capability under TTFields. Gene expression analysis of GBM tissues obtained before and after patients’ treatment with chemoradiation or chemoradiation+TTFields, demonstrated, in TTFields treated patients, increases of transcripts associated with antitumoral responses (CD8, NKp46, GranzymeB, Perforin), and decreases in protumoral-associated myeloid-compartment transcripts (CD66b, CD163, HLADR)
CONCLUSIONS
All antitumoral T cell functions examined, with the exception of proliferation, were unhindered by TTFields. Our findings warrant the further preclinical and clinical investigation into the combination of TTFields and immunotherapy. |
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ISSN: | 1522-8517 1523-5866 |
DOI: | 10.1093/neuonc/noy148.574 |