Image courtesy of NIAID
New research has revealed a population of T cells associated with relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplant (allo-SCT).
Patients experienced an increase in this cell population before their relapse was diagnosed clinically.
The cells also appear to be markers of T-cell exhaustion, which suggests therapies targeting T-cell exhaustion might be able to treat or prevent AML relapse after
allo-SCT.
Hong Zheng, MD, PhD, of Penn State University College of Medicine in Hershey, Pennsylvania, and her colleagues conducted this research and reported the results in Blood Cancer Journal.
The investigators noted that T cells are major players in the graft-vs-leukemia effect, but persistent antigen stimulation can lead to T-cell exhaustion.
To determine whether T-cell exhaustion is involved in relapse after allo-SCT, the team performed phenotypic and functional studies on T cells from the peripheral blood of AML transplant recipients.
Dr Zheng and her colleagues discovered that patients who relapsed after allo-SCT had significantly elevated levels of PD-1hiTIM-3+ T cells.
These T cells produced fewer cytokines—interleukin 2, tumor necrosis factor-α, and interferon-γ—than normal T cells, which is a sign of T-cell exhaustion.
In addition, while other T cells mostly consisted of all 4 T-cell subsets, PD-1hiTIM-3+ T cells had no naive T cells (CCR7+CD45RA+) and significantly decreased levels of terminally differentiated effector T cells (CCR7-CD45RA+).
The investigators said this suggests PD-1hiTIM-3+ cells are phenotypically antigen-experienced T cells that have lost functional subsets, which is consistent with a state of T-cell exhaustion.
The team believes their findings could pave the way for new treatments for AML patients undergoing allo-SCT.
The PD-1 inhibitor nivolumab has been shown to block T-cell exhaustion in patients with solid tumors. So Dr Zheng is planning a clinical trial to see if such treatment could work for AML patients as well.
She also believes that PD-1hiTIM-3+ T cells could be used to diagnose relapses earlier than is currently possible.
“Two months before we were able to clinically diagnose relapse in these patients, we found these markers elevated in them,” Dr Zheng said. “If we can have an early diagnostic marker, we will potentially be able to improve clinical outcome significantly.”
Dr Zheng is currently investigating the trigger for T-cell exhaustion in transplant recipients with AML.
“The hypothesis is that when you have chronic antigen stimulation, the T cell can get exhausted,” she said. “We think that residual leukemia in our patients is the chronic stimulator that causes this.”
