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T cell optimization for graft-versus-leukemia responses
Melinda A. Biernacki, … , Vipul S. Sheth, Marie Bleakley
Melinda A. Biernacki, … , Vipul S. Sheth, Marie Bleakley
Published May 7, 2020
Citation Information: JCI Insight. 2020;5(9):e134939. https://doi.org/10.1172/jci.insight.134939.
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T cell optimization for graft-versus-leukemia responses

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Abstract

Protection from relapse after allogeneic hematopoietic cell transplantation (HCT) is partly due to donor T cell–mediated graft-versus-leukemia (GVL) immune responses. Relapse remains common in HCT recipients, but strategies to augment GVL could significantly improve outcomes after HCT. Donor T cells with αβ T cell receptors (TCRs) mediate GVL through recognition of minor histocompatibility antigens and alloantigens in HLA-matched and -mismatched HCT, respectively. αβ T cells specific for other leukemia-associated antigens, including nonpolymorphic antigens and neoantigens, may also deliver an antileukemic effect. γδ T cells may contribute to GVL, although their biology and specificity are less well understood. Vaccination or adoptive transfer of donor-derived T cells with natural or transgenic receptors are strategies with potential to selectively enhance αβ and γδ T cell GVL effects.

Authors

Melinda A. Biernacki, Vipul S. Sheth, Marie Bleakley

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Figure 1

Overview of allogeneic hematopoietic cell transplantation, including cellular components of an unmanipulated T cell–replete peripheral blood stem cell (PBSC) graft.

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Overview of allogeneic hematopoietic cell transplantation, including cel...
Key cellular components of the hematopoietic graft are indicated by pictograms, including αβ T cells (CD4+CD3+, green; CD8+CD3+, blue; Tn are indicated in lighter colors and Tm darker) and γδ T cells (gray with TCR). The green bar indicates the approximate time frame in which patients receive immunosuppressive medications for prevention and/or treatment of GVHD. Blue bars indicate usual periods of risk for post-HCT complications: light blue indicates early post-HCT risks primarily related to conditioning, darker blue indicates later post-HCT risks related primarily to immunosuppression and GVHD. Gray shading indicates the primary origin of relapse protection at different times after HCT: in the first 12 months due to conditioning therapy (dark gray), and after 12 months due to donor-derived GVL responses (lighter gray). Illustrated by Rachel Davidowitz.

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