2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.02C.01 Investigating the Role of VISTA Immune Checkpoint in Human and Murine Mesothelioma Cell Lines

EP.02C.01 Investigating the Role of VISTA Immune Checkpoint in Human and Murine Mesothelioma Cell Lines

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The study explored the role of the VISTA immune checkpoint in human and murine mesothelioma (MM) cell lines. VISTA, known for its inhibitory effect on T-cell proliferation, also appears to inhibit tumor-specific T-cell activity. However, its exact role in mesothelioma remains unclear. This research aimed to determine how VISTA is regulated and how its silencing affects MM biology. The hypothesis posited that VISTA expression might be controlled by MAPK and AKT pathways, which are consistently active in MM cells. Inhibiting these pathways could offer therapeutic strategies in combination with immune checkpoint blockade.<br /><br />Western blotting and flow cytometry were used to assess VISTA expression in several mesothelioma cell lines. Knockdown experiments using siRNA demonstrated successful suppression of VISTA in both human and murine cells, leading to reductions in ERK1/2 and AKT phosphorylation in HAY mesothelioma cells, suggesting that VISTA might influence downstream signaling pathways.<br /><br />The research also tested the effects of MEK inhibition using the drug Trametinib. It was found that in H2373 cells, Trametinib inhibited ERK1/2 phosphorylation but paradoxically increased AKT phosphorylation and VISTA expression. Meanwhile, in epithelioid mesothelioma cells (HAY), MEK/ERK inhibition led to decreased VISTA expression, highlighting differences in response between cell types.<br /><br />The study concluded that VISTA interacts with ERK/AKT signaling pathways. The inhibition of these pathways influenced VISTA expression differently depending on the MM cell subtype. These findings suggest that VISTA could be a potential target in MM treatment strategies, although its varied responses imply a more complex role in tumor biology.

Asset Subtitle

Abishek Sehgal

Meta Tag

Speaker Abishek Sehgal

Topic Tumor Biology – Preclinical Biology

Keywords

VISTA

immune checkpoint

mesothelioma

T-cell proliferation

MAPK pathway

AKT pathway

ERK1/2 phosphorylation

Trametinib

MEK inhibition

tumor biology