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

Abstract

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. 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. 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). Ever smoking was associated with increased odds of IgA in ovarian tumors. 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.