Bone Marrow-derived CD8 + T Cells From Pediatric Leukemia Patients Express PD1 and Expand Ex Vivo Following Induction Chemotherapy

摘要

Adoptive cell therapy (ACT) of chimeric antigen receptor T cells has demonstrated remarkable success for the treatment of pediatric B-cell leukemia. For patients who are not candidates for chimeric antigen receptor T-cell therapy, ACT using tumor antigen-experienced polyclonal T cells may be a treatment option. Since leukemic blasts reside in the bone marrow and bone marrow is a preferred site for homeostatic proliferation of cytotoxic memory CD8~(+)T cells, we hypothesized that bone marrow would be a source of activated T cells. The aim of this study was to determine the feasibility of using bone marrow-derived T cells following postinduction chemotherapy for use in adoptive cell transfer. Matched patient samples of bone marrow and peripheral blood-derived T cells expanded ex vivo and displayed similar apoptotic profiles. Before activation and expansion, there was a significant increase in the percentage of bone marrow-derived CD8~(+)T cells expressing activation markers PD1, CD45RO, and CD69 as compared with peripheral blood CD8~(+)T cells. Considering, melanoma-reactive CD8~(+)T cells reside in the subset of PD1~(+)CD8~(+)T cells, the bone marrow may be an enriched source leukemic-specific T cells that can be used for ACT.