2022 World Conference on Lung Cancer (Posters)-P1.14-04. Silencing ADAR1 Abrogates Mesothelioma Tumourigenicity

Pdf Summary

This study investigated the role of ADAR1 in mesothelioma tumorigenicity. ADAR1 is a protein that promotes cancer development and growth. Previous studies have shown that inhibition of ADAR1 improves response to immune therapy and delays tumor growth in melanoma and colon cancer models. In mesothelioma, ADAR1 is highly expressed and may contribute to resistance to immunotherapies. <br /><br />The researchers silenced ADAR1 in human and murine mesothelioma cells using targeted siRNA or CRISPR/Cas9 deletion. Silencing of ADAR1 resulted in impaired tumor growth and increased sensitivity to immune checkpoint inhibitors and oncolytic therapies. <br /><br />The study also found that stimulation with IFNβ induced the p150 isoform of ADAR1 in mesothelioma cells, and silencing of ADAR1 decreased IFNβ secretion. ADAR1 knockout in both human and murine mesothelioma cell lines did not affect the in vitro growth rate. <br /><br />In animal models, ADAR1 knockout cells showed a significant decrease in tumorigenicity compared to parental cells. The loss of tumorigenicity was observed in both immunocompetent and athymic mice. The addition of an extracellular matrix did not restore tumor formation. <br /><br />No difference in tumor response was observed between ADAR1 knockout and parental cells in response to PD-L1 targeted therapy or oncolytic virus therapy administered individually. However, further experiments combining these treatments are planned. <br /><br />In conclusion, silencing of ADAR1 suppresses mesothelioma tumorigenicity and increases sensitivity to immune checkpoint inhibitors and oncolytic therapies. The mechanisms underlying the loss of tumorigenicity and the potential for combination therapies with PD-L1 inhibitors and oncolytic viruses are still being investigated.

Asset Subtitle

Robert Kratzke, United States

Meta Tag

Speaker Robert Kratzke, United States

Topic Mesothelioma, Thymoma, and Other Thoracic Malignancies - Preclinical

Keywords

ADAR1

mesothelioma

tumorigenicity

cancer development

immune therapy

tumor growth

inhibition

melanoma

colon cancer

immunotherapies