Epigenetic therapy strengthens immune synapses to potentiate susceptibility of lung cancer cells to adoptive γδ T cell therapy [seq]

Purpose: Epigenetic drug DNA methyltransferase inhibitors (DNMTis) are immunomodulating agents that may sensitize cancer cells to immune cell attack. However, it is still unclear how DNMTi affects cancer cells to the killing by immune cells. We therefore try to uncover the alternations of genomic DNA methylation, chromatin accessibility and transcriptomes after DNMTi treatment of cancer cells. Methods: Six human lung cancer cell lines (A549, H1299, CL1-0, CL1-5, H1792, PC9) treated without (Mock) or with 100 nM decitabine (DAC) for 72 hours followed by growing in drug-free medium for three days were subjected to mRNA-seq and Omni-ATAC-seq analyses. Results: mRNA-seq and ATAC-seq analyses reveal upregulation of actin and intermediate filament, and downregulation of microtubule modules by decitabine in human lung cancer cell lines. Conclusion: Decitabine primes lung cancer cells to γδ T cell-mediated killing through regulating cytoskeleton associated genes potentially involved in immune synapse formation. mRNA-seq and ATAC-seq analyses of control (Mock) and decitabine (DAC) treated human lung cancer cell lines.