Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Immunol Invest. 2020 May;49(4):365-385. doi: 10.1080/08820139.2019.1661429. Epub 2019 Sep 19.

Abstract

In cancer or hematologic disorders, chemokines act as growth- or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, -9, -10, CCL2, -5, and IL-12 in AML/MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blast-proportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, -9, -10 and lower release of CCL2 and -5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2-release at relapse were found compared to first diagnosis - pointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, -9, -10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and -5 but lower levels of CXCL8, -9, -10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, -9, -10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

Keywords: Dendritic cells; T-cells; acute myeloid leukemia; chemokines; immunotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cytokines / blood*
  • Female
  • Humans
  • Immunotherapy
  • Leukemia, Myeloid, Acute / blood*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Stem Cell Transplantation

Substances

  • Cytokines