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

// Frida Ewald Sander 1 , Anna Rydström 1 , Elin Bernson 1 , Roberta Kiffin 1 , Rebecca Riise 1 , Johan Aurelius 1,2 , Harald Anderson 3 , Mats Brune 2 , Robin Foà 4 , Kristoffer Hellstrand 1 , Fredrik B. Thorén 1 and Anna Martner 1 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.