High expression of B7-H3 on stromal cells defines tumor and stromal compartments in epithelial ovarian cancer and is associated with limited immune activation

• DOI: 10.1186/s40425-019-0816-5
• Publication Date: 2019-12-31T12:02:22Z
• Authors: Heather L. MacGregor; Azin Sayad; Andrew Elia; Ben X. Wang; Sarah Rachel Katz; Patricia A. Shaw; Blaise A. Clarke; Sarah Q. Crome; Celine Robert-Tissot; Marcus Q. Bernardini; Linh T. Nguyen; Pamela S. Ohashi
• Keywords: Immune checkpoint

<h3>Background</h3> B7-H3 and B7-H4 are highly expressed by many human malignancies making them attractive immunotherapeutic targets. However, their expression patterns immune contexts in epithelial ovarian cancer have not been well characterized. <h3>Methods</h3> We used flow cytometry, immunohistochemistry, genomic analyses to determine the of B7-H3, B7-H4, PD-L1 tumor, stromal, cells tumor microenvironment (TME). analyzed cell frequency PD-1, TIM3, LAG3, ICOS, TIA-1, granzyme B, 2B4, CD107a, GITR on T cells; CD20, CD22, IgD, BTLA, CD27 B CD16 monocytes; PD-L1, PD-L2, ICOSL, CD40, CD86, CLEC9a antigen-presenting cytometry. determined intratumoral cellular location using immunohistochemistry. compared differences infiltration tumors with low or high tumor-to-stroma ratio from same unrelated patients. <h3>Results</h3> On non-immune cells, was restricted whereas both stromal cells. Stromal TME levels this differential assess found that associated increased monocytes, frequencies PD-1^high CD8⁺ APCs, decreased APCs. CD86 APCs proportion CD4⁺ were strongly correlated within patient, CD40 ICOSL not. <h3>Conclusions</h3> This study provides insight into TME. Further, we demonstrate an association between phenotype tumor-infiltrating also find some but all parameters show consistency peritoneal metastatic sites. These data implications for design immunotherapies targeting these B7 molecules cancer.