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.

中文翻译：

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嗜酸性粒细胞的积累预测了用免疫检查点抑制剂对黑素瘤治疗的反应。

嗜酸性粒细胞已被鉴定为黑色素瘤免疫治疗的预后标志物，并提示其有助于抗肿瘤宿主防御。但是，对免疫检查点抑制剂（ICI）对嗜酸性粒细胞的影响研究很少。在这里，我们应用常规实验室测试，多色流式细胞仪，RNA微阵列分析和生物复合测定法分析了32例接受pembrolizumab或nivolumab和ipilimumab联合治疗的患者的循环嗜酸性粒细胞和相关血清炎症因子。我们证明对ICI治疗的临床反应与外周血嗜酸性粒细胞积累有关。此外，免疫疗法导致嗜酸性粒细胞遗传和激活特征的改变。发现ICI治疗期间血清IL-16浓度升高与外周血嗜酸性粒细胞频率增加有关。使用免疫组织化学，我们观察到嗜酸性粒细胞脱粒增强，并且嗜酸性粒细胞与ICI治疗的黑色素瘤患者肿瘤组织的CD8 + T细胞浸润之间呈正相关。我们的发现突出了ICI效应的其他机制，并提出嗜酸性粒细胞水平是可能受益于这种免疫疗法的黑色素瘤患者的新型预测标志物。