Ovarian cancer tumor immune profiles associated with intrauterine device and oral contraceptive use

Abstract Background Non-hormonal intrauterine devices (IUDs) create an inflammatory uterine environment while oral contraceptives (OC) suppress ovulation and have different associations with ovarian cancer risk. We have evaluated the associations of these two contraceptive exposures with ovarian tumor immune infiltration. Methods This study assessed associations of IUD and OC use with tumor immune features via multiplex immunofluorescence in 24 ovarian tumor tissue microarrays from four case-control and two cohort studies. Multivariable-adjusted beta-binomial models estimated the odds of tumor T cell positivity by contraceptive history. Results High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3 + mean=3.4%, SD = 6.1) and each T cell subtype. Ever (vs. never) IUD use was modestly associated with increased cytotoxic T cell infiltration (CD3 + CD8 + OR:1.14, 95% CI:0.99–1.32), which was stronger among those with a history of endometriosis, postmenopausal women, and smokers. Conversely, OC use ≥1 year (vs. never) was associated with lower cytotoxic T cell odds (CD3 + CD8 + OR:0.89, 95% CI:0.79–1.00; p -het=0.008). Increased odds of terminal T cell exhaustion were observed for IUD use only (CD3 + PD1 + TIM3 + OR:1.53, 95% CI:0.99–2.36), which was stronger among those who had ever used genital powder or BMI > 25 kg/m 2 . Conclusions Pre-diagnostic contraception use may influence ovarian tumor immunity and may modulate cancer susceptibility.