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Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia

Journal article
Authors Frida Ewald Sander
Anna Rydström
Elin Bernson
Roberta Kiffin
Rebecca E Riise
Johan Aurelius
H. Anderson
Mats Brune
R. Foa
Kristoffer Hellstrand
Fredrik Bergh Thorén
Anna Martner
Published in Oncotarget
Volume 7
Issue 7
Pages 7586-7596
ISSN 1949-2553
Publication year 2016
Published at Sahlgrenska Cancer Center
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 7586-7596
Language en
Links dx.doi.org/10.18632/oncotarget.7210
Keywords acute myeloid leukemia, immunotherapy, cytotoxic T cells, antigen-specific T cells, Immunology and, histamine dihydrochloride, transplantation, memory, differentiation, interleukin-2, lymphocytes, maintenance, remission, responses, effector, Oncology, Cell Biology
Subject categories Clinical Medicine

Abstract

Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8(+) (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distribution of cytotoxic T cells was observed comprising a reduction of T effector memory cells and a concomitant increase of T effector cells. The dynamics of T cell subtypes during immunotherapy prognosticated relapse and survival, in particular among older patients and remained significantly predictive of clinical outcome after correction for potential confounders. Presence of CD8(+) T cells with specificity for leukemia-associated antigens identified patients with low relapse risk. Our results point to novel aspects of T cell-mediated immunosurveillance in AML and provide conceivable biomarkers in relapse-preventive immunotherapy.

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