open access

https://hdl.handle.net/2115/93015

Blocking of oestrogen signals improves anti-tumour effect regardless of oestrogen receptor alpha expression in cancer cells

英語

2023-10-05

Springer Nature

British journal of cancer

129(6)

935-946

BackgroundAnti-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.MethodsUsing a clinical dataset, immune cells of humans and mice, female mice with and without ovaries, and several murine ER & alpha;-negative cancer cell lines, we evaluated the effect of oestrogen on immunity in TME.ResultsClinical 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.ConclusionsThis 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' ER & alpha; expression.

学術雑誌論文

Accepted Manuscript

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41416-023-02381-0

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