Immunotherapy after complete remission in acute myeloid leukemia (AML) is associated with decreasing levels of regulatory T-cells, which leads to favorable clinical outcomes, according to research published in Cancer Immunology, Immunotherapy (published online July 18, 2017; doi:10.1007/s00262-017-2040-9).
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Regulatory T-cells are known for harboring diverse immunosuppressive functions, thus promoting cancer progression. Recent studies have shown that the depletion of regulatory T-cells or strategies to target their immunosuppressive features significantly reduce cancer growth. However, further research is needed to validate this finding.
Anna Martner, Sahlgrenska Cancer Center, University of Gothenburg (Sweden), and colleagues conducted a phase IV trial to assess regulatory T-cell levels during immunotherapy in patients with AML in complete remission. A total of 84 patients (aged 18-79 years) underwent ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of disease. The study aimed to identify the features, functions, and dynamics of regulatory T-cells during immunotherapy and to determine the potential impact of regulatory T-cells on relapse risk and survival.
Researchers observed a significant increase in regulatory T-cell counts in peripheral blood during initial cycles of HDC and IL-2. Accumulating regulatory T-cells, they wrote, were similar to thymic-derived natural regulatory T-cells, showed heightened expression of CTLA-4, and suppressed the cell cycle proliferation of conventional T-cells in an ex vivo setting.
Furthermore, researchers asserted that relapse of AML could not be prognosticated by regulatory T-cell counts at baseline or after the initial cycle of HDC and IL-2. After subsequent immunotherapy cycles, the magnitude of regulatory T-cell induction was diminished. Exploratory analyses implied that reduced induction of regulatory T-cells in later treatment cycles was significantly associated with a favorable clinical outcome.
“Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive regulatory T-cells that may be targeted for improved anti-leukemic efficiency,” the authors concluded. Further research is needed to evaluate alternative approaches of minimizing the negative impact of regulatory T-cells in AML, including replacing the IL-2 component of therapy with modified IL-2 variants or IL-15.—Zachary Bessette
