Efficient Ex Vivo Expansion of γδ T-Cells from AML Patients Requires Elimination of Circulating Leukemic Blasts

Ana Caterina Parente-Pereira, Pramila Krishnamurthy, Lynsey Whilding, Kyriaki Ioannou, Sara Ciprut, Victoria Potter, Ghulam Mufti, Linda Barber, Farzin Farzaneh, John Maher

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Abstract

γδ T-cells play an important role in immune surveillance of acute myeloid leukemia (AML). The main circulating subtype expresses a Vγ9Vδ2 T-cell receptor and may be expanded ex vivo following aminobisphosphonate activation. While such
protocols operate robustly in healthy donors, they are often inefficient using blood samples from patients with advanced malignancy. In keeping with this, we found that when leukemic blasts were present in peripheral blood samples, culture of γδ T-cells from patients with AML was unsuccessful. By contrast, expansion proved much more effective after chemotherapy-mediated clearance of circulating blasts, yielding similar γδ T-cell numbers to healthy donors. This principle was confirmed using serial samples obtained from the same patients. Importantly, expanded γδ T-cells were functional, indicated by bisphosphonate-potentiated anti-leukemic activity and cytokine release in vitro. These preliminary findings suggest a therapeutic potential for γδ T-cells, given that they can be readily expanded from AML patients in therapy induced remission.
Original languageEnglish
Pages (from-to)28-33
JournalAdvances in Leukemia Research and Treatment
Volume2
Issue number1
Publication statusPublished - 28 Dec 2020

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