WASHINGTON, D.C. – Scientists are uncovering new clues about how immunotherapy might work against a stubborn blood cancer, acute myeloid leukemia (AML). The treatment appears to alter the environment where cancer cells reside, potentially making the immune system’s job easier.
Unlocking Treatment Mysteries
In a study published in July in Science Advances, researchers examined bone marrow from adults with relapsed or refractory AML. This form of the disease is notoriously difficult to treat and often carries a grim prognosis. For these patients, the cancer had either returned after treatment or never responded in the first place.
The study involved treating patients with two drugs: pembrolizumab, which helps the immune system target cancer cells, and decitabine, which influences gene activity. While not every patient saw a benefit, some showed signs of immune cells becoming active in the bone marrow. This prompted scientists to dig deeper into why.
A Cellular Neighborhood Watch
Using sophisticated tools like single-cell spatial transcriptomics, a team analyzed individual cells within the bone marrow samples. This technique allowed researchers to pinpoint where genes were active and map the precise locations of RNA molecules within each cell.
This high-resolution view revealed that in some patients, immune cells moved closer to leukemia cells following treatment. This suggests the immune system was attempting to engage. The study also noted changes in cell communication patterns, hinting at how the treatment might disrupt cancer’s ability to evade immune detection.
“Our findings show how immunotherapy may shift the types of cells found in the neighborhood around leukemia cells,” said Gege Gui, the study’s first author and a research scientist at the Fralin Biomedical Research Institute Cancer Research Center in Washington, D.C. At the time of the research, Gui was also a doctoral student at Johns Hopkins University.
“That gives us clues about how the immune system and cancer interact – and how we might help patients by advancing our understanding of underlying biological mechanisms.”
Christopher Hourigan, director of the Fralin Biomedical Research Institute Cancer Research Center in Washington, D.C., and a senior author, emphasized the value of such detailed analysis.
I am impressed by the potential of the careful work Dr. Gui has done integrating powerful computational approaches with these novel genomic tools. Too often cancer therapy doesn’t work as well as we would like for patients with AML, but research like this is getting us to a stage where we can start understanding why that may be so that we can hopefully design better treatments in the future.
Christopher Hourigan, Director, Fralin Biomedical Research Institute Cancer Research Center
Hourigan, also a professor at the Fralin Biomedical Research Institute and the Virginia Tech Carilion School of Medicine, is an oncologist and physician-scientist specializing in translational medicine and precision oncology. Laura Dillon, a research associate professor at the Fralin Biomedical Research Institute Cancer Research Center in Washington, D.C., also contributed to the research.
This collaborative effort spanned multiple leading research institutions. Kasper Hansen from Johns Hopkins University provided expertise in statistical genomics and computational analysis. Chen Zhao from the National Cancer Institute at the National Institutes of Health contributed insights into tumor immunology and advanced tissue imaging.
