1420 Understanding racial differences in the ovarian cancer tumor microenvironment

Background

Ovarian cancer is frequently diagnosed in the advanced stages. These patients usually respond to standard therapy initially, but about eighty percent soon become resistant to platinum based treatments and die within five years.^{1 2} Also importantly, the overall survival of African American (black) women with high grade serous ovarian cancer (HGSOC) is worse than for Caucasian (white) women.^{3 4} This is partly due to socioeconomic discrepancies but the biology of the ovarian tumor microenvironment (TME) may also be a major contributing factor to dispartate outcomes between these patient groups. Here we will test the hypothesis that there are differing immune and gene parameters in black and white patients ovarian TME which may predispose black patients to worse survival.

Methods

To understand differences between the ovarian TME in patients of different races we used two different methods. Firstly, studies investigated ovarian tumor sections of black and white HGSOC patients. Formalin fixed paraffin embedded (FFPE) sections were stained by immunohistochemistry (IHC) for CD8+ T cells and for myeloid derived suppressor cells (MDSC; CD11b+CD14+CD33+ co-staining by multiplex immunofluorescence). CD8+ T cells in ovarian cancer tissue sections were scored in a semi-quantitative manner using the H-score, which incorporates percentage of cells stained and intensity of staining resulting in a score ranging from 0 lowest to 300 highest. A pilot study was also conducted by NanoString Digital Spatial Profiling to compare differences in gene expression in tissue arrays of black and white HGSOC patients TME.

Results

There was a trend towards a lower CD8+ T cell H-score in black patients (70.9, n=8) than in white patients (83.9, n=9) in the ovarian TME, although this difference was non-significant. There were no significant differences in MDSC density in tumors between black and white patients. There were several differentially expressed genes in the ovarian TME of black versus white patients in CD3, CD68 and PanCK ROIs (figure 1).

Conclusions

It is known that an increased presence of CD8+ T cells in the ovarian TME is associated with improved ovarian cancer outcome.⁵ Testing in a larger patient cohort will determine whether there is a significantly different density or distribution of CD8+ T cells between black and white patients in the ovarian TME. Studies are in progress to validate the differentially expressed genes between black and white patients and to correlate with grade of ovarian cancer and survival.

References

1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17–48. doi: 10.3322/caac.21763 2. Liu L, Xiong W. Effect of molecular targeted agents in chemotherapy for treating platinum-resistant recurrent ovarian cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2021;100:e26849. doi: 10.1097/MD.0000000000026849 3. Srivastava, et al. Racial health disparities in ovarian cancer: not just black and white. J. Ovarian Res. 2017;10:58-y. 4. Hildebrand JS, et al. Racial disparities in treatment and survival from ovarian cancer. Cancer Epidemiol. 2019;58:77–82. 5. Sato E, Olson SH, Ahn J, Bundy B, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 2005;102:18538–18543.