Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors

Oncoimmunology. 2020 Feb 15;9(1):1727116. doi: 10.1080/2162402X.2020.1727116. eCollection 2020.

Abstract

Eosinophils have been identified as a prognostic marker in immunotherapy of melanoma and suggested to contribute to anti-tumor host defense. However, the influence of immune checkpoint inhibitors (ICI) on the eosinophil population is poorly studied. Here, we applied routine laboratory tests, multicolor flow cytometry, RNA microarray analysis, and bio-plex assay to analyze circulating eosinophils and related serum inflammatory factors in 32 patients treated with pembrolizumab or the combination of nivolumab and ipilimumab. We demonstrated that clinical responses to ICI treatment were associated with an eosinophil accumulation in the peripheral blood. Moreover, immunotherapy led to the alteration of the eosinophil genetic and activation profile. Elevated serum concentrations of IL-16 during ICI treatment were found to be associated with increased frequencies of eosinophils in the peripheral blood. Using immunohistochemistry, we observed an enhanced eosinophil degranulation and a positive correlation between eosinophil and CD8+ T cell infiltration of tumor tissues from melanoma patients treated with ICI. Our findings highlight additional mechanisms of ICI effects and suggest the level of eosinophils as a novel predictive marker for melanoma patients who may benefit from this immunotherapy.

Keywords: Melanoma; T cells; eosinophils; immune checkpoint inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Eosinophils*
  • Humans
  • Immune Checkpoint Inhibitors
  • Ipilimumab / therapeutic use
  • Melanoma* / drug therapy
  • Nivolumab / therapeutic use

Substances

  • Immune Checkpoint Inhibitors
  • Ipilimumab
  • Nivolumab

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project number 259332240/RTG 2099 (to J. Utikal and V. Umansky) and the Cooperation between German Cancer Research Center (DKFZ) and Ministry of Science, Technology and Space of Israel (MOST) in Cancer Research (CA181 to V. Umansky). This work was kindly backed by the COST Action BM1404 Mye-EUNITER (www.mye-euniter.eu). COST is supported by the EU Framework Program Horizon 2020.