Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sci Adv. 2024 Sep 27;10(39):eadp2442. doi: 10.1126/sciadv.adp2442.
Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if estrogens affect eosinophil biology in tumors and how this influences ICB efficacy has not been determined. Here, we report that estrogens decrease the number of peripheral eosinophils and TATE, and this contributes to increased tumor growth in validated murine models of breast cancer and melanoma. Moreover, estrogen signaling in healthy female mice also suppressed peripheral eosinophil prevalence by decreasing the proliferation and survival of maturing eosinophils. Inhibiting estrogen receptor (ER) signaling decreased tumor growth in an eosinophil-dependent manner. Further, the efficacy of ICBs was increased when administered in combination with anti-estrogens. These findings highlight the importance of ER signaling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of ER modulators to increase ICB efficacy in multiple tumor types.
雌激素调节哮喘和其他炎症性疾病中的嗜酸性粒细胞增多症。此外，外周血嗜酸性粒细胞增多和肿瘤相关组织嗜酸性粒细胞增多（TATE）预测乳腺癌对免疫检查点阻断（ICB）的反应更好。然而，雌激素如何以及是否影响肿瘤中的嗜酸性粒细胞生物学，以及这如何影响 ICB 的疗效尚未确定。在这里，我们报告雌激素减少外周血嗜酸性粒细胞和 TATE 的数量，这导致乳腺癌和黑色素瘤的已验证小鼠模型中的肿瘤生长增加。此外，健康雌性小鼠中的雌激素信号通过减少成熟嗜酸性粒细胞的增殖和存活来抑制外周血嗜酸性粒细胞的流行。抑制雌激素受体（ER）信号以嗜酸性粒细胞依赖性方式降低肿瘤生长。此外，当与抗雌激素联合使用时，ICB 的疗效增加。这些发现强调了 ER 信号作为调节嗜酸性粒细胞生物学和 TATE 的重要性，并强调了 ER 调节剂的潜在近期临床应用，以增加多种肿瘤类型的 ICB 疗效。
