The local immune cell environment of uterine fibroids: a systematic review

Uterine fibroids are benign tumours of the myometrium. For large and/or multiple fibroids, there are no fertility-sparing pharmacological therapies. Better understanding of fibroid pathophysiology is key to developing such treatments. Current understanding of the pathophysiology of fibroid development has largely centred on hormone dependent growth and regression. The uterus is highly immunologically active, and pathological lesions from other benign uterine conditions exhibit local differences in immune cell populations compared to neighbouring analogous tissue. Characterising the differences in the local immune cells between fibroid tissue and non-diseased myometrium will inform understanding of fibroid pathophysiology and future therapeutic targets. This systematic review synthesises current evidence on the immune cell presence within uterine fibroids. Existing studies suggest a trend towards increased macrophage infiltration in fibroid tissue compared to matched myometrium, and reduced macrophage presence following hormonal therapy. There are conflicting reports on fibroid leucocyte and mast cell populations. Only a limited number of studies investigated a broader panel of immune cells, including dendritic, natural killer and T cells. Considerable methodological heterogeneity was observed across studies, alongside a frequent lack of demographic reporting, and variable use of matched fibroid-adjacent and healthy myometrial controls. To better characterise the immunological environment of uterine fibroids and the hormonal mechanisms that may govern it, future studies should employ standardised methodology, comprehensive immune cell panels and larger sample sizes that are segregated by menstrual cycle phase.