Cancers driven by hiccups in RNA processing can’t hide from our immune system, according to new work published today in Cell. A cross-institutional team Fred Hutch Cancer Center and Memorial Sloan Kettering Cancer Center (MSK) found that common splicing factor mutations in myelodysplastic syndrome or acute myeloid leukemia cells create tell-tale, cancer-specific molecular “typos” that sharp-eyed immune cells can read.
The collaborators also isolated, for the first time, immune cells that can recognize and kill leukemia cells with these genetic misspellings while leaving healthy cells unharmed.
The Fred Hutch and MSK scientists hope their findings lay the foundation for an off-the-shelf cellular immunotherapy for patients with MDS or AML driven by these splicing factor mutations.
“We’re able to find natural features of the cancer themselves that are targetable,” said Fred Hutch RNA splicing expert and co-senior author Robert Bradley, PhD, who holds the McIlwain Family Endowed Chair in Data Science. “It’s exciting because it’s a new way of thinking about how the immune system can recognize cancers: It doesn’t have to just come from lots of mutations in the tumor.”
