Background <p>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&#xa0;these two contraceptive exposures with ovarian tumor immune infiltration.</p> Methods <p>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.</p> Results <p>High-grade serous tumors had the highest percentage of tumor cells positive for total T cells (CD3<sup>+</sup> 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<sup>+</sup>CD8<sup>+</sup> 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<sup>+</sup>CD8<sup>+</sup> OR:0.89, 95% CI:0.79–1.00; <i>p</i>-het=0.008). Increased odds of terminal T cell exhaustion were observed for IUD use only (CD3<sup>+</sup>PD1<sup>+</sup>TIM3<sup>+</sup> OR:1.53, 95% CI:0.99–2.36), which was stronger among those who had ever used genital powder or BMI &gt; 25 kg/m<sup>2</sup>.</p> Conclusions <p>Pre-diagnostic contraception use may influence ovarian tumor immunity and may modulate cancer susceptibility.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

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

  • Jennifer M. Mongiovi,
  • Ana Babic,
  • Naoko Sasamoto,
  • Mary K. Townsend,
  • Allison F. Vitonis,
  • Mollie Barnard,
  • Jonathan Hecht,
  • T. Rinda Soong,
  • Jose R. Conejo-Garcia,
  • Lauren C. Peres,
  • Joellen M. Schildkraut,
  • Holly R. Harris,
  • Jennifer A. Doherty,
  • Francesmary Modugno,
  • Brooke L. Fridley,
  • Shelley S. Tworoger,
  • Kathryn L. Terry

摘要

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/m2.

Conclusions

Pre-diagnostic contraception use may influence ovarian tumor immunity and may modulate cancer susceptibility.