title: Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia.
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.
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Frida Ewald
authors: FE
authors: Sander
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Anna
authors: A
authors: Rydström
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Elin
authors: E
authors: Bernson
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Roberta
authors: R
authors: Kiffin
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Rebecca
authors: R
authors: Riise
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.|Department of Hematology, University of Gothenburg, Gothenburg, Sweden.
authors: Johan
authors: J
authors: Aurelius
authors: Department of Cancer Epidemiology, University of Lund, Lund, Sweden.
authors: Harald
authors: H
authors: Anderson
authors: Department of Hematology, University of Gothenburg, Gothenburg, Sweden.
authors: Mats
authors: M
authors: Brune
authors: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.
authors: Robin
authors: R
authors: Foà
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Kristoffer
authors: K
authors: Hellstrand
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Fredrik B
authors: FB
authors: Thorén
authors: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
authors: Anna
authors: A
authors: Martner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006632:Histamine / Q000008:administration & dosage; D017442:Histamine Agonists / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D017442:Histamine Agonists; D007376:Interleukin-2; D006632:Histamine
keywords: Immune response; Immunity; Immunology and Microbiology Section; acute myeloid leukemia; antigen-specific T cells; cytotoxic T cells; immunotherapy