Abstract 3008: Association between distress and the tumor immune microenvironment in women with ovarian cancer
Authors: Hathaway Cassandra A. , Townsend Mary K. , Conejo-Garcia Jose R. , Fridley Brooke L. , Segura Carlos Moran , Nguyen Jonathan V. , Sasamoto Naoko , Saeed-Vafa Daryoush , Terry Kathryn L. , Kubzansky Laura D. , Tworoger Shelley S. 
Published: April 2023

Abstract
Various forms of distress, most notably depression, increase ovarian cancer risk. Prior work suggests depression can lead to systemic immune suppression; moreover, after ovarian cancer diagnosis, ongoing depression can lower tumor T cell infiltration. Here, we evaluated the relationship between pre-diagnosis depression and the ovarian tumor immune microenvironment.
Analyses were conducted among women with ovarian cancer in the Nurses’ Health Study (NHS; n=250), NHSII (n=122) and New England Case-Control Study (NEC; n=215). Self-report of depressive symptoms, antidepressant use, or physician diagnosis were used to define depression status. Multiplex immunofluorescence assays were performed on tumor tissue microarrays to measure infiltration of T cells, immune checkpoints, B cells, and immunoglobulins in the tumor area. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for positivity of tumor immune cells using a beta-binomial model within a repeated measures framework comparing those with and without depression.
Depression was not associated with abundance of CD3+ T cells, CD3+CD8+ cytotoxic T cells, or CD3+CD4+ T helper cells. However, we observed significantly increased odds of having recently activated cytotoxic (CD3+CD8+CD69+) and exhausted T cells (CD3+Lag3+) in tumors of women with vs. without depression (OR=1.34, 95%CI=1.08-1.65 and OR=1.25, 95%CI=1.02-1.53, respectively). Associations were comparable considering only high grade serous tumors (comparable ORs=1.31, 95%CI=1.04-1.65 and OR=1.25, 95%CI=1.00-1.56, respectively). No associations were observed for total B cells (CD19+) and naïve or memory B cells (CD20+). However, there were significantly decreased odds of having tumor infiltrating plasma cells (CD138+) in women with vs. without depression (OR=0.54, 95%CI=0.33-0.89). Among high grade serous carcinomas, the association with plasma cells was similar, though not statistically significant, and depression was related to decreased odds of having naïve and memory B cells (OR=0.56, 95%CI=0.32-0.97) and increased odds of IgG (OR=1.26, 95%CI=1.01-1.58).
Unexpectedly, we observed that immune cells indicative of T cell activation were higher in ovarian tumors of depressed vs. non-depressed women. This may be due to increased inflammation in women with depressive symptomology. Conversely, analyses of plasma cells suggested a reduced adaptive tumor immune response for women with vs. without depression. These results suggest depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment and that interventions to improve distress in ovarian cancer patients may be a potential strategy to improve outcomes.
Citation Format: Cassandra A. Hathaway, Mary K. Townsend, Jose R. Conejo-Garcia, Brooke L. Fridley, Carlos Moran Segura, Jonathan V. Nguyen, Naoko Sasamoto, Daryoush Saeed-Vafa, Kathryn L. Terry, Laura D. Kubzansky, Shelley S. Tworoger. Association between distress and the tumor immune microenvironment in women with ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3008.