Lifetime Exposure to Cigarette Smoke, B-Cell Tumor Immune Infiltration, and Immunoglobulin Abundance in Ovarian Tumors

Abstract

Abstract Background: Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the impact of smoke exposure across the life-course on B-cell infiltration and Ig abundance in ovarian tumors. Methods: We measured markers of B and plasma cells and Ig isotypes using multiplex immunofluorescence on 395 ovarian cancer tumors in the Nurses’ Health Study (NHS)/NHSII. We conducted beta-binomial analyses evaluating odds ratios (OR) and 95% confidence intervals (CI) for positivity of immune markers by cigarette exposure among cases and Cox proportional hazards models to evaluate hazard ratios (HR) and 95% CI for developing tumors with low (<median) or high (≥median) immune cell/Ig percentage. Results: There were no associations between smoke exposure and B-cell or IgM infiltration in ovarian tumors. Among cases, we observed higher odds of IgA+ among ever smokers (OR, 1.54; 95% CI, 1.14–2.07) and ever smokers with no parental smoke exposure (OR, 2.03; 95% CI, 1.18–3.49) versus never smokers. Women with parental cigarette smoke exposure versus not had higher risk of developing ovarian cancer with low IgG+ (HR, 1.51; 95% CI, 1.10–2.09), whereas ever versus never smokers had a lower risk (HR, 0.74; 95% CI, 0.56–0.99). Conclusions: Ever smoking was associated with increased odds of IgA in ovarian tumors. Impact: IgA has been associated with improved ovarian cancer outcomes, suggesting that although smoking is associated with poor outcomes in patients with ovarian cancer, it may lead to improved tumor immunogenicity.