Associations between Parity, History of Breastfeeding, and T-cell Profile of Ovarian Tumors.

BACKGROUND: Parity and breastfeeding are associated with systemic changes in maternal inflammation and reduced risk of ovarian cancer, but little is known about their impact on the ovarian tumor immune microenvironment. METHODS: We evaluated the associations of self-reported parity and history of breastfeeding with tumor-infiltrating T cells among 1,706 ovarian carcinoma cases with tumor tissue collected across four studies. The abundance of tumor-infiltrating T cells was measured by multiplex immunofluorescence in tumor tissue microarrays. ORs and 95% confidence intervals (CI) for the positivity of tumor immune cells were calculated using beta-binomial models and stratified by histotype. RESULTS: Compared with ovarian tumors in nulliparous women, there was no association between parity and ovarian tumor T-cell abundance among all histotypes combined but suggestion of increased cytotoxic T cells and T-cell exhaustion among parous women with clear-cell tumors. When restricted to parous women, history of breastfeeding was associated with increased odds for all T-cell types [i.e., total T, cytotoxic T, helper T (Th), regulatory T, and exhausted T cells], with ORs ranging from 1.11 to 1.42. For every 6 months of breastfeeding, we observed increased odds of activated Th-cell infiltration (CD3+CD4+CD69+; OR, 1.13, 95% CI, 0.99-1.29), with a similar association for high-grade serous tumors, but lower odds in clear-cell tumors (OR, 0.43, 95% CI, 0.21-0.87). CONCLUSIONS: History of breastfeeding may alter the ovarian tumor immune microenvironment by modulating the abundance of tumor-infiltrating T cells. IMPACT: Although replication is required, history of breastfeeding may play a role in the activation of the ovarian tumor immune response.