Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors

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, multico...

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Main Authors: Sonja C. S. Simon, Xiaoying Hu, Jasper Panten, Mareike Grees, Simon Renders, Daniel Thomas, Rebekka Weber, Torsten J. Schulze, Jochen Utikal, Viktor Umansky
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:OncoImmunology
Subjects:
Online Access:http://dx.doi.org/10.1080/2162402X.2020.1727116
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author Sonja C. S. Simon
Xiaoying Hu
Jasper Panten
Mareike Grees
Simon Renders
Daniel Thomas
Rebekka Weber
Torsten J. Schulze
Jochen Utikal
Viktor Umansky
author_facet Sonja C. S. Simon
Xiaoying Hu
Jasper Panten
Mareike Grees
Simon Renders
Daniel Thomas
Rebekka Weber
Torsten J. Schulze
Jochen Utikal
Viktor Umansky
author_sort Sonja C. S. Simon
collection DOAJ
description 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.
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spelling doaj.art-929050eefb31430384cff2eee14ffd5e2022-12-21T20:38:29ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17271161727116Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitorsSonja C. S. Simon0Xiaoying Hu1Jasper Panten2Mareike Grees3Simon Renders4Daniel Thomas5Rebekka Weber6Torsten J. Schulze7Jochen Utikal8Viktor Umansky9German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)Heidelberg UniversityGerman Cancer Research Center (DKFZ)German Cancer Research Center (DKFZ)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.http://dx.doi.org/10.1080/2162402X.2020.1727116melanomaimmune checkpoint inhibitorseosinophilst cells
spellingShingle Sonja C. S. Simon
Xiaoying Hu
Jasper Panten
Mareike Grees
Simon Renders
Daniel Thomas
Rebekka Weber
Torsten J. Schulze
Jochen Utikal
Viktor Umansky
Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
OncoImmunology
melanoma
immune checkpoint inhibitors
eosinophils
t cells
title Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
title_full Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
title_fullStr Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
title_full_unstemmed Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
title_short Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
title_sort eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors
topic melanoma
immune checkpoint inhibitors
eosinophils
t cells
url http://dx.doi.org/10.1080/2162402X.2020.1727116
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AT xiaoyinghu eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT jasperpanten eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT mareikegrees eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT simonrenders eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT danielthomas eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT rebekkaweber eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT torstenjschulze eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT jochenutikal eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors
AT viktorumansky eosinophilaccumulationpredictsresponsetomelanomatreatmentwithimmunecheckpointinhibitors