Inflammatory-related Risk Factors and the Abundance of Immune Cells in the Tumor Microenvironment among Black and White Women with High-grade Serous Ovarian Cancer 公开

Abstract

Background

Ovarian cancer is a lethal gynecologic malignancy, ranking fifth in cancer deaths among women. Inflammatory-related risk factors and immune cell abundance in tumor immune microenvironment (TIME) were associated with survival of high-grade serous ovarian cancer (HGSOC), respectively. The effects of inflammatory-related risk factors on HGSOC were hypothesized to be mediated through TIME. Black women have a poorer survival compared to White women. Survival differences may be explained by the different associations of inflammatory-related risk factors and TIME.

Methods

121 Black women and 121 White women with HGSOC were selected from North Carolina Ovarian Cancer Study (NCOCS) and African American Cancer Epidemiology Study (AACES). Inflammatory-related factors were determined using survey data and the inflammation-related risk score (IRRS) was calculated. The abundance of tumor infiltrating lymphocytes (TILs), cytotoxic T-cells, regulatory T-cells (Tregs), myeloid cells, and neutrophils in TIME were measured by multiplex immunofluorescence. The immunoscore, representing the density and location of TILs and cytotoxic T-cells, was calculated. Unconditional logistic regression and polytomous logistic regression were conducted to determine the relationships of inflammatory-related risk factors and IRRS with immune cell abundance and immunoscore in the overall population and stratified by race, respectively.

Results

In the overall population, significant associations between the inflammatory-related exposures and immune cell abundance in TIME include talc use and higher total TILs (OR=1.74, 95% CI: 1.03-2.95), fibroids and higher tumoral cytotoxic T-cells (OR=2.17, 95% CI: 1.16-4.07), acetaminophen use and higher total myeloid cells (OR=4.52, 95%CI: 1.01-20.27), and higher IRRS and lower total neutrophils (OR=0.55, 95% CI: 0.31-0.98). Other non-significant patterns were observed, such as higher BMI in young adulthood or measured within 5 years prior to diagnosis and higher immune cell abundance. The descriptive analysis and regression analysis indicated racial differences in the prevalence of exposures and their associations with immune cell abundance in TIME.

Conclusion

In this exploratory analysis, the effect of inflammatory-related risk factors on survival of HGSOC may be mediated by immune cell abundance in TIME in the overall population, but this association differed according to race.

Table of Contents

Abstract iv

Acknowledgement vi

List of tables vii

Table of contents viii

Background and significance 1

Methods 13

Results 18

Discussion 26

References 33

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Women's Studies Health Sciences, Obstetrics and Gynecology Health Sciences, Epidemiology
关键词	immune cell abundance high-grade serous ovarian cancer tumor microenvironment inflammatory-related risk factors racial disparity
Committee Chair / Thesis Advisor	Joellen M. Schildkraut, Emory University
Committee Members	Lauren C. Peres, Moffitt Cancer Center

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