Robert Manguso, PhD

Kathleen Yates

Collins Cheruiyot, PhD

A core challenge of cancer treatment is the high adaptability of cancer cells.

Sometimes, even when tumor cells come under attack from the immune system—facing an inflamed, overall hostile environment—they are still able to survive, and even thrive. However, these harsh conditions also rewire tumor cells in specific ways, changing their internal states and gene activity.

In a recent study by lead author Collins Cheruiyot, PhD, and co-senior authors Kathleen Yates and Robert Manguso, PhD, of Mass General Brigham and the Broad Institute of MIT and Harvard, scientists studied these changes to better understand if they could be targeted to make cancer treatments more effective.

Using eight lab-based mouse cancer models, they exposed tumor cells to immune signaling proteins to mimic immune stress. With the help of CRISPR gene editing, they then systematically turned off different genes to identify which genes the cells relied on to adapt.

They found that when certain genes—including those encoding the GPI transamidase complex and FITM2—were edited out, tumor cells fared worse when exposed to immune signals. In fact, they were pushed into severe stress, which in some cases led to tumor cell death. The researchers confirmed these findings in mice, where without these genes, immune checkpoint blockade drugs were more effective.

The authors conclude it’s possible to take advantage of how tumor cells change to survive immune attack and exploit these vulnerabilities to improve cancer treatment and immunotherapies.

Published in Nature Genetics on June 9, 2026 | Read the paper: “Inflammatory cytokines induce new cancer dependencies”

Summary reviewed by: Collins Cheruiyot, PhD, lead author; Kathleen Yates and Robert Manguso, PhD, co-senior authors