Research Papers: Immunology:
Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia
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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
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
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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