At a glance:
New study in mice reveals how tumors modify their own gene activity to evade immune detection and outlines which genes are affected.
Authors suggest such gene editing is a common defense mechanism across cancers.
Work offers a roadmap for designing improved cancer immunotherapies that override the genetic changes.
It’s become clear that tumors can modify their own genes to evade detection and attack by the immune system. A new study in mice reveals how these changes happen and identifies for the first time a comprehensive list of the genes affected.
The work, led by Harvard Medical School researchers at Beth Israel Deaconess Medical Center and Boston Children’s Hospital, provides a roadmap for developing therapies that override these genetic changes and restore the immune system’s ability to fight cancer.
“No one had done an unbiased study of this before, because by the time a tumor becomes detected it has already finished gene editing,” said Judy Lieberman, HMS professor of pediatrics at Boston Children’s and co-senior author of the study with Winston Hide, HMS associate professor of pathology at Beth Israel Deaconess.
The findings, published in Nature Immunology, indicate that tumors edit the activity of multiple genes to avoid immune recognition. But the team also shows a way to override these edits and curb tumor growth in a mouse model of breast cancer, which is notoriously resistant to immunotherapy.
Authorship, funding, disclosures
Ying Zhang of PCMM (now at Peking University) and Pourya Naderi Yeganeh of Beth Israel are co-first authors of the study. Additional authors are Haiwei Zhang, Simon Yuan Wang, Zhouyihan Li, Bowen Gu, Dian-Jang Lee, Zhibin Zhang, Athanasios Ploumakis, Ming Shi, Hao Wu, and Eric Lieberman Greer.
Lieberman is based in the Program in Cellular and Molecular Medicine (PCMM) at Boston Children’s. Hide is co-director of the Non-Coding RNA Precision Diagnostics and Therapeutics Core Facility at Beth Israel Deaconess.
The work was supported by the National Institutes of Health (grants R01CA240955, K99CA255841, DP2AG055947), a Charles King fellowship, and a Cancer Research Institute fellowship.
The authors declare no competing interests.