A new study by an international group of researchers, including those from Children’s Hospital of Philadelphia (CHOP), has found that acute myeloid leukemia (AML) ages and exhausts immune cells, impairing their ability to fight off cancer. Researchers found that patients with a greater proportion of these aged immune cells in their blood had worse responses to chemotherapy and immunotherapy and lower overall survival.
AML is the most aggressive form of blood cancer and is difficult to treat, with a high relapse rate; only 1 in 5 patients survive more than five years after diagnosis. Although immunotherapies have revolutionized the treatment of other blood cancers, so far using a similar approach to treating AML has had little success.
Studying tumor samples from nearly 2,000 patients with AML, the researchers identified a genetic signature of immune dysfunction in these patients, characterized by T cell aging and exhaustion. They found that patients with highly exhausted T cells had a far worse response to chemotherapy than those with lower levels of T cell dysfunction: on average, their survival was seven months shorter. These patients were also less likely to respond to immunotherapy, surviving for just over four months while those with low levels of exhaustion survived for more than 15.
“These findings have important implications for the treatment of children, adolescents, and adults with AML, particularly when it comes to identifying patients who might respond successfully to immunotherapy,” said study co-author Sarah K. Tasian, MD, Associate Professor of Pediatrics and Chief of the Hematologic Malignancies Program at Children’s Hospital of Philadelphia. “Future research will also endeavor to identify ways of reinvigorating aging and exhausted immune cells in patients with AML, which could lead to more successful treatment.”
Learn more about this study, which was led by Dr. Sergio Rutella at Nottingham Trent University and Dr. Leo Luznik at Johns Hopkins University and was recently published in the Journal of Clinical Investigation.
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A new study by an international group of researchers, including those from Children’s Hospital of Philadelphia (CHOP), has found that acute myeloid leukemia (AML) ages and exhausts immune cells, impairing their ability to fight off cancer. Researchers found that patients with a greater proportion of these aged immune cells in their blood had worse responses to chemotherapy and immunotherapy and lower overall survival.
AML is the most aggressive form of blood cancer and is difficult to treat, with a high relapse rate; only 1 in 5 patients survive more than five years after diagnosis. Although immunotherapies have revolutionized the treatment of other blood cancers, so far using a similar approach to treating AML has had little success.
Studying tumor samples from nearly 2,000 patients with AML, the researchers identified a genetic signature of immune dysfunction in these patients, characterized by T cell aging and exhaustion. They found that patients with highly exhausted T cells had a far worse response to chemotherapy than those with lower levels of T cell dysfunction: on average, their survival was seven months shorter. These patients were also less likely to respond to immunotherapy, surviving for just over four months while those with low levels of exhaustion survived for more than 15.
“These findings have important implications for the treatment of children, adolescents, and adults with AML, particularly when it comes to identifying patients who might respond successfully to immunotherapy,” said study co-author Sarah K. Tasian, MD, Associate Professor of Pediatrics and Chief of the Hematologic Malignancies Program at Children’s Hospital of Philadelphia. “Future research will also endeavor to identify ways of reinvigorating aging and exhausted immune cells in patients with AML, which could lead to more successful treatment.”
Learn more about this study, which was led by Dr. Sergio Rutella at Nottingham Trent University and Dr. Leo Luznik at Johns Hopkins University and was recently published in the Journal of Clinical Investigation.
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