The MYC oncogene can suppress inflammatory signaling

genome instability is a hallmark of many aggressive cancers, including triple-negative breast cancers (TNBCs). TNBCs do not respond to hormone receptor-targeted treatment, and unfortunately, also do not respond well to recently developed immune checkpoint inhibitors.
Black with image of divinding cells

The lack of response to immune checkpoint inhibitors is surprising, since the massive genomic instability in TNBCs triggers inflammatory signaling, which was associated with response to immune checkpoint inhibitor treatment in other tumor types.

In this study, we investigated inflammatory signaling in TNBCs, and discovered that the MYC oncogene (which is frequently amplified in TNBC) can suppress inflammatory signaling. Specifically, we revealed that MYC, together with its cofactor MIZ1, can suppress the expression of key genes in the interferon pathway. Through this mechanisms, MYC amplification leads to a depletion of immune cells in the TNBC micro-environment and could explain why TNBCs can fly under the radar of the immune system.

Our results establish MYC expression as a determinant of immune escape and response to immune checkpoint inhibition, and warrant follow-up studies to investigate MYC as a therapeutic target to potentiate immune checkpoint inhibitors.

This work was the result of a close collaboration with the lab of Jos Jonkers at the Netherlands Cancer Institute (NKI-AvL, Amsterdam) and Rudolf Ferhmann.

For more information, check the link to the article:

MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling