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

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

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.

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

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Histamine / administration & dosage
  • Histamine Agonists / administration & dosage
  • Humans
  • Immunotherapy*
  • Interleukin-2 / administration & dosage
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Remission Induction
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Histamine Agonists
  • Interleukin-2
  • Histamine

Associated data

  • ClinicalTrials.gov/NCT01347996