Abstract 4696: Characterizing CD39 and CD73 cell subtypes in the tumor microenvironment using MultiOmyx

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.4696-4696
• Main Authors: Todorov, Courtney, Gallagher, Kevin, Wortman, Juliana, Nunns, Harry, Parnell, Erinn, Leones, Eric, Yeung, Elaine, Russell, Blair, Sahafi, Flora, Au, Qingyan
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-4696

CD39 and CD73 are membrane bound enzymes that function together to convert extracellular adenosine 5’-triphospate (ATP)/adenosine diphosphate (ADP) into adenosine. CD39 first catalyzes ATP/ADP into adenosine monophosphate (AMP), which is then converted by CD73 into adenosine. Accumulation of extracellular adenosine creates an immunosuppressive tumor environment and facilitates tumor growth and metastasis. Conversely, the presence of ATP promotes a pro-inflammatory, tumor-suppressive environment. Suppression of CD73/CD39 activity and reduction of extracellular adenosine has been shown to support an antitumor immune response. Therefore, the targeting of CD73 and CD39, both individually as well as in combination with immune checkpoint inhibitors for biomarkers such as PD-1 and CTLA-4, is an emerging strategy for cancer therapeutics. CD73/CD39 have been described in multiple cell types, including tumor cells, fibroblasts, endothelial cells, tumor infiltrating lymphocytes (TILs), myeloid cells, and natural killer (NK) cells. While known to be expressed on multiple cell types, the spatial characterization of CD39 and CD73 in the tumor microenvironment (TME) is still poorly understood. Characterizing the diversity of active CD73 and CD39 populations in the tumor environment will help improve development of targeted therapies for cancer treatment. The multiplex immunofluorescence (mIF) platform MultiOmyx will be used to define the distinct populations of cells expressing CD73 and/or CD39 in the TME. MuliOmyx is a proprietary mIF platform for the visualization and characterization of up to 60 protein biomarkers in a single FFPE section. Herein we report the design and use of a novel panel of commercially-available antibodies broad enough to characterize CD39 and CD73 subpopulations in the TME of a variety of tumor indications including lung, prostate, and colon cancer. Using this panel in combination with proprietary deep-learning based image analysis, CD39 and CD73 positive cells can be characterized into different immune and TME subtypes. Understanding of the variety and phenotype of CD39 and CD73 expressing cells in the TME is crucial to define the populations being targeted by therapies for cancer treatment. Citation Format: Courtney Todorov, Kevin Gallagher, Juliana Wortman, Harry Nunns, Erinn Parnell, Eric Leones, Elaine Yeung, Blair Russell, Flora Sahafi, Qingyan Au. Characterizing CD39 and CD73 cell subtypes in the tumor microenvironment using MultiOmyx. [a