Study reveals how cancer thwarts immunity and how to potentially turn the tables

A new study by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Boston Children’s Hospital and published in Natural immunology shows how tumors grow by avoiding the immune system.

Researchers have revealed how tumor genes modify themselves to evade detection by the immune system. The study identifies, for the first time, the genes that tumors actually silence, offering a roadmap for better immunotherapies.

The researchers studied breast cancer in a mouse model, using genome-wide single-cell RNA sequencing to identify genes that tumors modify during their development. The team found that tumors use epigenetic modification, particularly DNA methylation, to suppress genes involved in the innate immune response, the body’s first line of defense against pathogens and disease.

It is through this silencing that most tumors evade current immunotherapies, such as CAR-T cells and checkpoint inhibitors. However, scientists have also discovered that the FDA-approved drug decitabine, a chemotherapy that slows the growth of cancer cells, can reverse these genetic changes.

At low doses, decitabine reactivates the immune response, leading to a reduction in tumor growth by increasing the presence of immune cells that attack the tumor.

The findings suggest that gene editing may be a common defense mechanism across a variety of cancers. Further research is needed to explore how this knowledge applies to other solid tumors such as lung and ovarian cancers. Future studies will focus on gene editing in patients with genetic predispositions to cancer, particularly in early tumor stages and during metastasis.

“Our research sheds light on the sophisticated strategies tumors use to hide from the immune system,” said Winston Hide, Ph.D., senior author of the study and co-director of the Non-Coding RNA Precision Diagnostics and Therapeutics Core Facility at BIDMC.

“By identifying the specific genes that tumors silence to escape detection, we are opening the door to new therapeutic approaches. These findings could lead to the development of more targeted immunotherapies, potentially improving outcomes for cancer patients.”