Identification of Transcriptional Regulators of Immune Evasion across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma

• DOI: 10.20944/preprints202410.1274.v1
• Publication Date: 2024-10-17T01:48:46Z
• Authors: Simran Venkatraman; Brinda Balasubram...; Pornpan Kongpracha; Supaporn Yangngam; Nisa Chuangchot; Suparada Khanaruk...; Suyanee Thongchot; Monthira Suntipar...; Kyaw Zwar Myint; Sunphahas Soodvilai; Tavan Janvilisri; Siwanon Jirawatan...; Chanitra Thuwajit; Jarek Meller; Somchai Chutipong...; Rutaiwan Tohtong
• Keywords: Evasion (ethics); Identification; Immune escape

Background: Immune evasion in cancer is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory checkpoint expression (IC). Recent developments have immunotherapies such as blockade (ICB) chimeric antigen receptor T-cell (CAR-T) therapy effectively impede this but benefit limited patient cohort. This investigation introduces systemic immunotherapeutic strategy by inhibition of master-regulators (MR-IE). Methods: We utilized the TCGA PanCancer Atlas transcriptomic data to subset stratify samples based on IC levels CIBERSORT estimate cell infiltration. Differential gene analysis was conducted unravel pathways associated with evasion. Transcription Factor Enrichment Analysis Survival identify rank candidate MR-IE per type. The top-ranking cholangiocarcinoma (CCA) validated for its regulation ICs using quantitative PCR western blots. Orbitrap Proteomics employed assess changes immune-related proteome CCA cells after inhibited or knocked-down. Lastly, viability immune-mediated death assessed combination fourth-generation anti-folate alpha (FRɑ) CAR-T therapy. Results: workflow ranked identified 33 tumor types. MYC high-ranking CCA. modulated PD-L1 adn key markers inflammation cells. Moreover, able potentiate mediated Conclusions: Cumulatively, these results offer list targets type can be further explored validated. study also highlights promise novel potent treatment