Cytokine alterations during paraneoplastic neutrophilia and leukemoid reaction in patients with advanced melanoma

Cancer Immunol Immunother. 2023 Feb;72(2):509-513. doi: 10.1007/s00262-022-03249-7. Epub 2022 Jul 16.

Abstract

Background: Paraneoplastic leukemoid reaction (PLR) is a rare phenomenon in metastasized melanoma associated with poor prognosis and rapid disease progression. Currently, no specific therapeutic options exist other than treating the underlying malignancy.

Methods: Five cases of paraneoplastic neutrophilia in patients with advanced-stage IV melanoma were enrolled in our study. Cytokine concentrations in patients' serum samples were analyzed before and during PLR using a multiplex cytokine array. Further, immunohistochemical staining of tumor tissue biopsied during PLR was performed.

Results and conclusions: We observed a strong correlation between worsening of tumor burden and aggravation of neutrophilia. Cytokine measurements revealed an increase of proinflammatory cytokines (IL6, IFNγ), proangiogenic cytokines (VEGF) and immune stem cell growth factors (G-CSF) during PLR. Immunohistochemistry confirmed neutrophil infiltration of tumor tissue. The presented cytokine alterations provide a basis for further functional analysis, which is necessary for the development of targeted therapeutic approaches against PLR.

Keywords: Cytokines; Inflammation; Melanoma; Neutrophils; Paraneoplastic leukemoid reaction.

MeSH terms

  • Cytokines
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Leukemoid Reaction* / complications
  • Leukocytosis
  • Melanoma* / complications
  • Neutrophils / metabolism
  • Prognosis

Substances

  • Cytokines
  • Granulocyte Colony-Stimulating Factor