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Oncotarget. 2016 Feb 16;7(7):7586-96. doi: 10.18632/oncotarget.7210.

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

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TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
Department of Hematology, University of Gothenburg, Gothenburg, Sweden.
Department of Cancer Epidemiology, University of Lund, Lund, Sweden.
Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.


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 (; 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.


Immune response; Immunity; Immunology and Microbiology Section; acute myeloid leukemia; antigen-specific T cells; cytotoxic T cells; immunotherapy

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