The immune landscape of uterine fibroids as determined by mass cytometry

Abstract

Objective

To study the differences in immune cell profiles in uterine fibroids (Fibs) and matched myometrium (Myo).

Design

Observational study.

Setting

Laboratory study.

Patient(s)

The study included tissue that was collected from 10 pairs of Fib and matched Myo from women, not on hormonal medications, undergoing hysterectomy and myomectomy.

Intervention(s)

None.

Main Outcome Measure(s)

Differences in immune cell and cytokine composition between Fib and matched Myo.

Result(s)

The mass cytometry analysis indicated that Fibs had a significantly higher number of natural killer (NK) cells, total macrophages, M2 macrophages, and conventional dendritic cells when compared with matched Myo from the same patient. In contrast, Fibs had significantly fewer CD3 and CD4 T cells when compared with Myo. The mass cytometry analysis results did not show any significant difference in the number of resting mast cells. Immunoflurorescent and immunohistochemical imaging confirmed the cytometry by time of flight results, showing a significantly higher number of NK cells, tryptase-positive mast cells indicative of mast cell activation, total macrophages, and M2 cells in Fibs and a significantly lower number of CD3 and CD4 T cells. The cytokine assay revealed significantly increased levels of human interferon α2, interleukin (IL)-1α, and platelet-derived growth factor AA and significantly lower levels of macrophage colony-stimulating factor and IL-1 receptor antagonist in Fib.

Conclusion(s)

Our results show significant differences in immune cell populations and cytokine levels between Fib and Myo. These differences could account for the increased inflammation in fib and a potential mechanism by which these tumors evade the immune system. These findings provide a foundation for further studies exploring the role of immune cells in Fib development.