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

SIMPLE SUMMARY: Immune checkpoint inhibitors, which stimulate the patient’s own T-cells to attack tumor cells, have revolutionized the treatment of metastatic melanoma. However, not all melanoma patients respond to therapy possibly due to a lack of T-cells present in or entering tumor tissue. It is presumed that eosinophils could aid T-cell-mediated immune response against tumor cells. In order to describe the local association of eosinophils and T-cells within the tumor microenvironment we investigated specific markers for cell type and activation status using immunofluorescence. Additionally, blood measurements were performed to determine the effects of eosinophil count and their activation status on the efficacy of immune checkpoint inhibition. There was a strong correlation between activated eosinophils and T-cells in melanoma. Furthermore, patients with high blood levels of activated eosinophils showed a delayed tumor progression. In the future, eosinophils may serve as prognostic biomarkers as well as novel therapeutic targets 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.