Myc Oncogene And Immune Detection Of Cancer

Activation of the Myc oncogene in cancer helps produce immune-suppressed conditions that aids in the evasion of tumor immune surveillance.

…we find that co-activation of Myc drives the immediate transition to highly proliferative and invasive adenocarcinomas marked by highly inflammatory, angiogenic, and immune-suppressed stroma. 

It therefore stands to reason that suppression if the Myc signaling can help restore anti-tumor immune function and that is what has been shown to occur, using agents that modify epigenetic changes in genes – changes that involve how the chromatin is modified (methylation, acetylation) instead of DNA sequence changes, with consequent alteration of gene expression. This is hopeful in the quest to improve anti-cancer immunotherapy.  Abstract:

Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.