Oncotarget

Research Papers: Immunology:

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

Frida Ewald Sander, Anna Rydström, Elin Bernson, Roberta Kiffin, Rebecca Riise, Johan Aurelius, Harald Anderson, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B. Thorén and Anna Martner _

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Oncotarget. 2016; 7:7586-7596. https://doi.org/10.18632/oncotarget.7210

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Abstract

Frida Ewald Sander1, Anna Rydström1, Elin Bernson1, Roberta Kiffin1, Rebecca Riise1, Johan Aurelius1,2, Harald Anderson3, Mats Brune2, Robin Foà4, Kristoffer Hellstrand1, Fredrik B. Thorén1 and Anna Martner1

1 TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden

2 Department of Hematology, University of Gothenburg, Gothenburg, Sweden

3 Department of Cancer Epidemiology, University of Lund, Lund, Sweden

4 Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy

Correspondence to:

Anna Martner, email:

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

Received: December 22, 2015 Accepted: January 26, 2016 Published: February 05, 2016

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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