针对具有雌激素敏感性癌细胞的乳腺癌患者，已经使用抗雌激素疗法。然而，对于没有雌激素敏感性肿瘤细胞的癌症患者中抗雌激素疗法在免疫细胞生物学中的潜在作用知之甚少。因此，我们旨在研究雌激素对肿瘤微环境中免疫的影响。通过使用临床数据集、人和小鼠的免疫细胞、有卵巢和无卵巢的雌性小鼠以及几种小鼠ERα阴性癌细胞系，我们评估了雌激素对肿瘤微环境中免疫的影响。临床数据分析表明，雌激素对CTL具有抑制性功效。此外，体外和体内实验揭示了雌激素在小鼠和人体内直接抑制肿瘤内CTL的作用；阻断雌激素信号会取消其免疫抑制作用，从而减少体内肿瘤生长。值得注意的是，免疫治疗（免疫检查点抑制剂；ICI）与抗雌激素疗法联合使用显示出显著的抗肿瘤效果。本研究对于雌激素如何促进肿瘤进展和阻断雌激素信号以增强ICI的抗肿瘤效果提供了新的见解，无论肿瘤细胞的ERα表达情况如何。©2023年。作者经Springer Nature Limited独家许可。

Anti-oestrogenic therapy has been used for breast cancer patients with oestrogen susceptibility cancer cells. However, little has been known about its potential role for immune cell biology within TME, particularly in cancer patients without oestrogen sensitivity of tumour cells. Therefore, we aimed to study the effect of oestrogen on immunity within TME.Using a clinical dataset, immune cells of humans and mice, female mice with and without ovaries, and several murine ERα-negative cancer cell lines, we evaluated the effect of oestrogen on immunity in TME.Clinical data analysis suggested oestrogen's suppressive efficacy against CTLs. Additionally, in vitro and in vivo experiments revealed intra-tumoural CTLs' direct repressive action by oestrogen in both mice and humans; blockade of oestrogen signals cancelled its immunosuppression resulting in tumour growth reduction in vivo. Most notably, immunotherapy (immune checkpoint inhibitor; ICI) combined with anti-oestrogenic therapy exhibited a dramatic anti-tumour effect.This study provides novel insights into how oestrogen contributes to tumour progression and a therapeutic rationale for blocking oestrogen signalling to boost the anti-tumour effect of ICI, regardless of tumour cells' ERα expression.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.