Abstract 3361: CD73 expression on tumor-infiltrating breast cancer leukocytes

Abstract

Abstract Recent studies have shown that CD73 could be a new promising target in breast cancer (BC). CD73 is a cell surface ecto-nucleotidase, expressed by both tumor cells and immune cells, that catalyses the hydrolysis of AMP into adenosine in the tumor microenvironment. Adenosine has immunosuppressive and tumor-promoting effects and is therefore implicated in the mechanism of tumor immune escape. High CD73 gene expression has recently been associated with a poor prognosis in triple negative BC. While tumor expression of CD73 is well documented, expression of CD73 on tumor-infiltrating immune cells remains poorly characterized. We evaluated the expression of CD73 on immune cells present in fresh tissue homogenates (GentleMACS with no enzymatic digestion) from untreated primary breast tumors and compared to its expression to peripheral blood mononuclear cells (PBMC) from patients with breast cancer. In the peripheral blood, CD73 was found mostly expressed on CD4+ (mean percentage: 13.24±12.88%) and CD8+T cells (mean percentage: 40.78±19.42%) and a major subset of B cells (mean percentage: 51.93±21.83%). Analysis of fresh tumor tissues revealed that less than 25% of CD45+ tumor immune infiltrates express CD73 (mean percentage: 17.63± 5,1%) and was relatively similar to its expression on PBMC (mean percentage: 14.87± 9.5%). In the tumor immune infiltrates, B cells were the immune subset with the higher proportion of CD73+ cells (mean percentage: 53.27±14.63%) while the proportion of CD73+ was lower on tumor-infiltrating CD8+ T cells compared to CD8+ PBMC (p value: 0.022). Notably, we observed that CD73 expression was significantly higher on tumor-infiltrating NK cells and CD14+ myeloid cells compared to peripheral cells (p = 0.005 for NK cells, and p = 0.015 for CD14+ cells). Immunofluorescence analysis confirmed that CD73 is expressed by both tumor cells, CD45+ immune cells and stromal cells in breast cancer. These results suggest that CD73 is differentially expressed on tumor-infiltrating leukocytes compared to PBMCs. Modulation of CD73 activity on tumor-infiltrating leukocytes may therefore contribute to the mechanism-of-action of anti-CD73 therapies. Citation Format: Laurence Buisseret, Soizic Garaud, Bertrand Allard, Isabelle Cousineau, Guillaume Chouinard, Christos Sotiriou, Karen Willard-Gallo, John Stagg. CD73 expression on tumor-infiltrating breast cancer leukocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3361. doi:10.1158/1538-7445.AM2015-3361