2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.03G.03 Tumor Treating Fields (TTFields) Induce Pro-Inflammatory Phenotype Skewing of Macrophages

Pdf Summary

This study by Novocure Ltd explores the immunomodulatory effects of Tumor Treating Fields (TTFields) on macrophages, a type of immune cell involved in tumor immunity. TTFields, known to disrupt cellular processes critical for cancer cell survival, were found to induce a pro-inflammatory phenotype in macrophages, promoting M1 polarization, which is associated with anti-tumor activity. <br /><br />The research demonstrated that TTFields could act similarly to lipopolysaccharides (LPS) in stimulating these immune cells, leading to enhanced expression of markers like CD80 and MHC-II, which are indicative of macrophage activation. TTFields promoted the secretion of cytokines and proteins such as CXCL1 and IL-6, which are linked to inflammatory responses, further reinforcing the pro-inflammatory state of M1 macrophages.<br /><br />Additionally, the study observed that TTFields influenced signaling pathways involved in immune activation. Specifically, the electric fields appeared to activate the GEF-H1/RhoA/ROCK/NFκB pathway, crucial in macrophage polarization and immune response regulation. This signaling led to increased levels of phosphorylated proteins such as p65, c-Jun, and GEF-H1, which are components of pathways known to modulate immune cell function.<br /><br />Overall, this research suggests that TTFields could enhance anti-tumor immunity by promoting a pro-inflammatory macrophage phenotype, potentially offering a novel approach to cancer immunotherapy by directly engaging the body's immune system to fight tumor cells. The findings also open up avenues for further investigation into the therapeutic applications of TTFields in treating cancers through immune modulation.

Asset Subtitle

Yiftah Barsheshet

Meta Tag

Speaker Yiftah Barsheshet

Topic Tumor Biology – Translational Biology

Keywords

Tumor Treating Fields

immunomodulatory effects

macrophages

M1 polarization

anti-tumor activity

cytokines

GEF-H1/RhoA/ROCK/NFκB pathway

immune activation

cancer immunotherapy

immune modulation