Specifically differentiated T cell subset promotes tumor immunity over fatal immunity

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Abstract

Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9IL-33 cells offers an attractive approach for separating GVL activity from GVHD.

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Ramadan, A., Griesenauer, B., Adom, D., Kapur, R., Hanenberg, H., Liu, C., … Paczesny, S. (2017). Specifically differentiated T cell subset promotes tumor immunity over fatal immunity. Journal of Experimental Medicine, 214(12), 3577–3596. https://doi.org/10.1084/jem.20170041

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