Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma

Abstract

Immune checkpoint inhibition (ICI) has yielded remarkable results in prolonging survival of metastatic melanoma patients but only a subset of individuals treated respond to therapy. Success of ICI treatment appears to depend on the number of tumor-infiltrating effector T-cells, which are known to be influenced by activated eosinophils. To verify the co-occurrence of activated eosinophils and T-cells in melanoma, immunofluorescence was performed in 285 primary or metastatic tumor tissue specimens from 118 patients. Moreover, eosinophil counts and activity markers such as eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) were measured in the serum before therapy start and before the 4th infusion of ICI in 45 metastatic unresected melanoma patients. We observed a positive correlation between increased tumor-infiltrating eosinophils and T-cells associated with delayed melanoma progression. High baseline levels of eosinophil count, serum ECP and EPX were linked to prolonged progression-free survival in metastatic melanoma. Our data provide first indications that activated eosinophils are related to the T-cell-inflamed tumor microenvironment and could be considered as potential future prognostic biomarkers in melanoma.

Pretreatment eosinophil count predicts response to atezolizumab plus bevacizumab therapy in patients with hepatocellular carcinoma

“…This value seems a little low, but we referred to a previous paper that reported eosinophil count as a biomarker for ICI treatment; cutoff value was 100 cells/μL in urothelial carcinoma and 130 cells/μL in melanoma. 10,18 Vaios et al reported that a high eosinophil count is associated with better PFS in patients receiving bevacizumab treatment for glioblastoma, which supports our findings. 28 Since there were reports that changes in eosinophil counts affect the prognosis of ICI treatment, we examined changes in eosinophil counts and prognosis, but they did not prove to be prognostic factors.…”

“…The normal eosinophil count is generally set at 100–300 cells/μL, and cutoff value of eosinophil we determined in the ATZ/BEV group was 170 cells/μL. This value seems a little low, but we referred to a previous paper that reported eosinophil count as a biomarker for ICI treatment; cutoff value was 100 cells/μL in urothelial carcinoma and 130 cells/μL in melanoma 10,18 . Vaios et al .…”

“…Increased eosinophil counts before and after ICI treatment have been reported to be associated with better prognosis. 18 In the ATZ/BEV group, 25patients (52.1%) had increased eosinophil counts. We compared PFS between ATZ/BEV-eosinophil-decreased group and ATZ/BEV-eosinophil-increased group, and there was no significant difference (Fig.…”

“…Increased eosinophil counts before and after ICI treatment have been reported to be associated with better prognosis 18 . In the ATZ/BEV group, 25patients (52.1%) had increased eosinophil counts.…”

Eosinophil may be a predictor of immune‐related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study

“…Mechanistically, microarray analysis using RNA isolated from eosinophils under ICI treatment in melanoma revealed that Wnt signaling prolongs the survival of activated eosinophils 34 . Activated eosinophils accumulate in tumor tissues, indicating that tumor‐infiltrating eosinophils eliminate cancer cells via vascular normalization and macrophage polarization 35–37 . Thus, despite reports on the functional analysis of eosinophils under ICI treatment, the detailed underlying mechanisms by which eosinophils are increased in peripheral blood and infiltrate into tumors have not been fully clarified.…”