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

• Published in: Journal of pediatric hematology/oncology Vol. 41; no. 8; pp. 648 - 652
• Main Authors: Palen, Katie, Thakar, Monica, Johnson, Bryon D, Gershan, Jill A
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-11-2019
• Subjects: Antigens, Differentiation - immunology; Apoptosis - immunology; Bone Marrow Cells - immunology; Bone Marrow Cells - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Child; Clinical and Laboratory Observations; Female; Gene Expression Regulation, Leukemic - immunology; Humans; Immunologic Memory; Induction Chemotherapy; Leukemia - drug therapy; Leukemia - immunology; Leukemia - pathology; Male; Neoplasm Proteins - immunology; Programmed Cell Death 1 Receptor - immunology
• ISSN: 1077-4114; 1536-3678
• DOI: 10.1097/MPH.0000000000001244

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.