CD39 Biomarker Identifies Exhausted T cells to Improve Immunotherapy

Project Overview

• Defining novel markers of exhaustion is important for identifying and reversing T cell exhaustion in immunotherapy.
• Dana-Farber scientists have developed a method for detecting and quantifying CD39 as diagnostically valuable marker of T cell exhaustion.
• Dana-Farber is looking for licensing opportunities for development of clinical assays for use in chronic viral infection and cancer immunotherapy settings. 

Technology

Exhausted T cells lose their ability to express multiple co-inhibitory molecules that impair their function, and limit immunity to chronic viral infection and efficacy of immunotherapy.

Despite extensive efforts to identify predictive markers of response to cancer immunotherapy, the portion of treated patients who respond to checkpoint inhibitors remains small. Therefore, a specific quantifiable indicator of exhausted T cells, such as CD39 levels, can be a valuable tool to guide clinical use of immune checkpoint therapy. 

The Dana-Farber team demonstrated that CD39 is a marker of exhausted CD8+ T cells. Specifically, CD8+ T cells that respond to chronic but not acute viral infections express high levels of CD39. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, coexpressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion, and correlates with viral load. The CD39 high CD8+ T cell population is enriched for cells with a phenotypic and functional profile of terminal exhaustion. 

Team Members: W. Nicholas Haining, BM, BCh, Arlene Sharpe, MD, PhD

Applications

CD39 levels, can be a valuable tool to guide clinical use of immune checkpoint therapy and also guide treatment decisions in chronic viral infections.

Opportunities

Dana-Farber is looking for licensing opportunities for development of clinical assays for use in chronic viral infection and cancer immunotherapy settings.