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Bone Marrow-derived CD8+ T Cells From Pediatric Leukemia Patients Express PD1 and Expand Ex Vivo Following Induction Chemotherapy. J Pediatr Hematol Oncol 2019 Nov;41(8):648-652

Date

06/19/2018

Pubmed ID

29912035

Pubmed Central ID

PMC6855330

DOI

10.1097/MPH.0000000000001244

Scopus ID

2-s2.0-85048631854 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

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 PD1CD8 T cells, the bone marrow may be an enriched source leukemic-specific T cells that can be used for ACT.

Author List

Palen K, Thakar M, Johnson BD, Gershan JA

Author

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antigens, Differentiation
Apoptosis
Bone Marrow Cells
CD8-Positive T-Lymphocytes
Child
Female
Gene Expression Regulation, Leukemic
Humans
Immunologic Memory
Induction Chemotherapy
Leukemia
Male
Neoplasm Proteins
Programmed Cell Death 1 Receptor