Acute and chronic B cell leukemia can promote T cell “exhaustion,” which contributes to increased susceptibility to infection and mortality. The treatment-independent mechanisms by which leukemia promotes T cell dysfunction are poorly understood, however.
Since metabolic pathways must be tightly regulated to allow normal T cell proliferation and function, Jeffrey Rathmell, Ph.D., Peter Siska, M.D., and colleagues at Duke University and the Netherlands reasoned that impaired T cell function in leukemia may result from altered metabolism.
In a study published last month in the Journal of Immunology, they show that T cells in leukemia patients and leukemia-bearing animals are metabolically suppressed partly through the upregulation of PD-1, which turns down T cell activation. Restoring T cell metabolism improved T cell function and delayed progression of leukemia.
Other studies have found that blockading PD-1 signaling can reactivate exhausted T cells in some solid tumors and in a mouse leukemia model. Modulation of T cell metabolism thus may represent a new therapeutic avenue for leukemia patients, they conclude.
The study was supported in part by National Institutes of Health grants CA183529 and DK105550.
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