2022 World Conference on Lung Cancer (ePosters)-EP16.01-016. Tumor Treating Fields (TTFields) Application Promotes a Pro-inflammatory Phenotype in Macrophages

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The document discusses the effects of Tumor Treating Fields (TTFields) on the polarization of macrophages, which are immune cells involved in inflammatory responses. TTFields are electric fields that disrupt the function of cancer cells. The study found that TTFields can alter the phenotype of macrophages, shifting them towards a pro-inflammatory state. This was observed in both M1-polarized macrophages (pro-inflammatory) and M2-polarized macrophages (anti-inflammatory). <br /><br />The researchers also investigated the underlying mechanisms behind these effects. They discovered that TTFields induced the phosphorylation of GEF-H1, a protein involved in macrophage polarization. This suggests that the GEF-H1/RhoA/ROCK pathway is involved in the phenotypic skewing of macrophages treated with TTFields. <br /><br />The study used bone marrow-derived macrophages (BMDMs) from mice and stimulated them with LPS/IFN-γ or IL-4 to polarize them towards the M1 or M2 phenotype, respectively. The BMDMs were then treated with TTFields using an in vitro system. Flow cytometry was used to analyze the expression of macrophage markers, and a multiplexed secretion assay was used to measure cytokine secretion. Western blotting was used to study the mechanism of action of TTFields on macrophages. <br /><br />The results showed that TTFields increased the expression of pro-inflammatory markers CD80 and MHC II in M1 macrophages. Furthermore, TTFields reduced the expression of M2 markers CD206 and ARG-1 in both M1 and M2 macrophages. The secretion profile of cytokines also shifted towards a pro-inflammatory pattern in M2 macrophages treated with TTFields. <br /><br />In conclusion, this study demonstrates that TTFields can modulate the phenotype of macrophages, promoting a pro-inflammatory state. The GEF-H1/RhoA/ROCK pathway appears to be involved in this process. These findings contribute to our understanding of the immunoregulatory effects of TTFields and may have implications for cancer treatment strategies.

Asset Subtitle

Moshe Giladi

Meta Tag

Speaker Moshe Giladi

Topic Tumour Biology and Biomarkers - Immune Biology & Immunotherapy

Keywords

Tumor Treating Fields

Macrophages

Inflammatory Responses

Phenotype

M1-polarized Macrophages

M2-polarized Macrophages

GEF-H1

RhoA

ROCK Pathway

Cancer Treatment Strategies